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Brink, Michel S., Anna W. Kersten, and Wouter G. P. Frencken. "Understanding the Mismatch Between Coaches’ and Players’ Perceptions of Exertion." International Journal of Sports Physiology and Performance 12, no. 4 (April 2017): 562–68. http://dx.doi.org/10.1123/ijspp.2016-0215.
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A mismatch between the training exertion intended by a coach and the exertion perceived by players is well established in sports. However, it is unknown whether coaches can accurately observe exertion of individual players during training. Furthermore, the discrepancy in coaches’ and players’ perceptions has not been explained.Purpose:To determine the relation between intended and observed training exertion by the coach and perceived training exertion by the players and establish whether on-field training characteristics, intermittent endurance capacity, and maturity status explain the mismatch.Methods:During 2 mesocycles of 4 wk (in November and March), rating of intended exertion (RIE), rating of observed exertion (ROE), and rating of perceived exertion (RPE) were monitored in 31 elite young soccer players. External and internal training loads were objectively quantified with accelerometers (PlayerLoad) and heart-rate monitors (TRIMPmod). Results of an interval shuttle-run test (ISRT) and age at peak height velocity (APHV) were determined for all players.Results:RIE, ROE, and RPE were monitored in 977 training sessions. The correlations between RIE and RPE (r = .58; P < .01) and between ROE and RPE (r = .64; P < .01) were moderate. The mean difference between RIE and RPE was –0.31 ± 1.99 and between ROE and RPE was –0.37 ± 1.87. Multilevel analyses showed that PlayerLoad and ISRT predicted RIE and ROE.Conclusion:Coaches base their intended and observed exertion on what they expect players will do and what they actually did on the field. When doing this, they consider the intermittent endurance capacity of individual players.
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Susilowati, Lolita Endang, Uyek Malik Yakop, Lestari Ujianto, and Bambang Hari Kusumo. "The Nutrient Uptake Efficiency, Crop Productivity and Quality of Rice Bean in Dry Land." JOURNAL OF TROPICAL SOILS 20, no. 1 (January 29, 2016): 1. http://dx.doi.org/10.5400/jts.2015.v20i1.1-9.
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Rice bean is a group of beans that are rich in carbohydrates, proteins and fats. This plant is resistant to pests and diseases, as well as the broad adaptability. This study aims to obtain an efficient fertilization pattern on rice bean cultivation in dry land. The treatments consisted of 9 fertilization patterns which were RP0: no fertilizer (control); RP1: 100% recommendation fertilizer (50 kg Urea and 100 kg SP-36 ha-1); RP2: 5 Mg ha-1 manure plus 50% recommendation fertilizer; RP3: RP2 plus MVA; RP4: 5 Mg ha-1 Crotalaria sp compost plus 50% recommendation fertilizer; RP5: RP4 plus VAM; RP6: 2.5 t ha-1 manure, 2.5 Mg ha-1 Crotalaria sp compost plus 50% recommendation fertilizer; RP7: 1.5 Mg ha-1 manure, 1 Mg ha-1 Crotalaria sp compost plus 50% recommendation fertilizer; RP8: RP7 plus MVA. Fertilization treatments were arranged in RCBD and each treatment was repeated 3 times. The fertilization treatments had no significant effect on NUE. Productivity of rice bean in RP3 and RP5 reached 3.75 Mg ha-1, in RP2 and RP4 achieved 2.64 Mg ha-1, and in the control treatment reached 1.94 Mg ha-1. Carbohydrate content in seeds increased by 20% in the fertilization treatments compared to the control. Protein and anthocyanin content in all treatments were not significantly different. The combination of 5 Mg organic fertilizer (manure and / or Crotalaria compost), 50% recommendation fertilizer plus MVA was an efficient fertilization pattern to improve P fertilizer uptake efficiency (PUE), productivity and quality of rice bean crop in dry land. [How to Cite: Lolita ES, UM Yakop, L Ujianto, and B Hari Kusumo. 2015. The Nutrient Uptake Efficiency, Crop Productivity and Quality of Rice Bean in Dry Land. J Trop Soils 19: 1-9. Doi: 10.5400/jts.2015.20.1.1][Permalink/DOI: www.dx.doi.org/10.5400/jts.2015.20.1.1]
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Soto, Juvenal, and Mark Aldrich. "RPE / RPE." Sirena: poesia, arte y critica 2006, no. 2 (2006): 130–33. http://dx.doi.org/10.1353/sir.2006.0171.
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Vinores, S. A., R. McGehee, A. Lee, C. Gadegbeku, and P. A. Campochiaro. "Ultrastructural localization of blood-retinal barrier breakdown in diabetic and galactosemic rats." Journal of Histochemistry & Cytochemistry 38, no. 9 (September 1990): 1341–52. http://dx.doi.org/10.1177/38.9.2117624.
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Breakdown of the blood-retinal barrier (BRB) is an early event in diabetic and galactosemic rats, but the location and nature of the specific defect(s) are controversial. Using an electron microscopic immunocytochemical technique, the retinas of normal, diabetic, and galactosemic rats were immunostained for endogenous albumin. Normal rats showed little evidence of BRB breakdown at either the inner barrier (retinal vasculature) or the outer barrier (retinal pigment epithelium) (RPE). In diabetic and galactosemic rats, as was true in human diabetics, BRB breakdown occurred predominantly at the inner BRB, but in some cases at the outer barrier as well. Treatment with the aldose reductase inhibitor sorbinil largely prevented BRB failure in galactosemic rats. In the inner retina of diabetic and galactosemic rats, albumin was frequently demonstrated on the abluminal side of the retinal capillary endothelium (RCE) in intercellular spaces, basal laminae, pericytes, ganglion cells, astrocytes, and the perinuclear cytoplasm of cells in the inner nuclear layer. Albumin did not appear to cross RCE cell junctions; however, it was occasionally seen in RCE cytoplasm of galactosemic rats. In the outer retina, albumin was frequently detected in the subretinal space, in the intercellular space between photoreceptors, and in the perinuclear cytoplasm of photoreceptor cells, but was only infrequently found in the RPE cells constituting the barrier. Albumin derived from the choroidal vasculature did not appear to cross the tight junctions of the RPE. These findings suggest that specific sites of BRB compromise are infrequent but that once albumin has crossed the RCE or RPE it freely permeates the retinal tissue by filling intercellular spaces and permeating the membranes of cells not implicated in BRB formation. The diffuse cytoplasmic staining of some RCE and RPE cells suggests that the predominant means of BRB breakdown in diabetes and galactosemia involves increased focal permeability of the surface membranes of the RCE and RPE cells rather than defective tight junctions or vesicular transport.
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Horner, Faye, James Wawrzynski, and Robert MacLaren. "Novel non-sense mutation in RP2 (c.843_844insT/p.Arg282fs) is associated with a severe phenotype of retinitis pigmentosa without evidence of primary retinal pigment epithelium involvement." BMJ Case Reports 12, no. 5 (May 2019): e224451. http://dx.doi.org/10.1136/bcr-2018-224451.
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Retinitis pigmentosa (RP) relates to a heterogeneous group of rod-cone dystrophies of varying genetic aetiology. There is currently great interest in gene replacement therapy. Phenotyping is of particular importance because some RP genes are expressed ubiquitously and it is critically important to understand which retinal layer is primarily affected. RP2 is increasingly diagnosed in patients suffering from X-linked RP, which causes outer retinal degeneration. We present a case of a previously unreported null mutation in RP2 associated with severe RP. Loss of the retinal pigment epithelium (RPE) was noted in the central macula but not around the disc or peripherally. There was therefore no evidence of independent degeneration of the RPE. Hence despite expression in all retinal cells, RP2 deficiency does not appear to be pathogenic to the RPE. This observation may be helpful in considering the promoter and route of delivery of adeno-associated viral gene therapy vectors encoding RP2.
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Xu, Z., S. Rafi, and W. Ramakrishna. "Polymorphisms and evolutionary history of retrotransposon insertions in rice promoters." Genome 54, no. 8 (August 2011): 629–38. http://dx.doi.org/10.1139/g11-030.
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Retrotransposons are ubiquitous in higher plant genomes. The presence or absence of retrotransposons in whole genome and high throughput genomic sequence (HTGS) from cultivated and wild rice was investigated to understand the organization and evolution of retrotransposon insertions in promoter regions. Approximately half of the Oryza sativa subsp. japonica ‘Nipponbare’ promoters with retrotransposons conserved in Oryza sativa subsp. indica ‘93-11’ and four wild rice species showed higher sequence conservation in retrotransposon than nonretrotransposon regions. We further investigated, in detail, the evolutionary dynamics of five retrotransposons in the promoter regions of 95 rice genotypes. Our data suggest that four of five insertions (Rp2–Rp5) occurred in the ancestor of AA genome, while the other insertion (Rp1) predates the ancestral divergence of Oryza officinalis (CC genome). Four retrotransposons (Rp2–Rp5) were present in 52% (Rp2), 29% (Rp3), 53% (Rp4), and 43% (Rp5) of the rice genotypes with AA genome type, and the fifth retrotransposon (Rp1) was present in 95% of the rice genotypes with AA, BBCC, or CC genome types. Furthermore, most of these retrotransposons were found to evolve slower than flanking promoter regions, suggesting a role in promoter function for regulating downstream genes.
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Pritchett, R. C., J. M. Green, T. R. Crews, R. Deere, D. C. Tucker, and J. R. McLester. "RPE." Medicine & Science in Sports & Exercise 35, Supplement 1 (May 2003): S287. http://dx.doi.org/10.1097/00005768-200305001-01598.
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Dwyer, Gregory B., Milchell H. Whaley, and Leonard A. Kaminsky. "FREQUENCY OF RPE INQUIRIES EFFECTS THE RPE." Journal of Cardiopulmonary Rehabilitation 12, no. 5 (September 1992): 360. http://dx.doi.org/10.1097/00008483-199209000-00059.
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Hornsby, Jared H., James M. Green, Eric K. O’Neal, Lauren L. Killen, Joyce R. McIntosh, and Tom E. Coates. "Influence of Terminal RPE on Session RPE." Journal of Strength and Conditioning Research 27, no. 10 (October 2013): 2800–2805. http://dx.doi.org/10.1519/jsc.0b013e3182830d6c.
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Demura, Shinichi, and Yoshinori Nagasawa. "Relations between Perceptual and Physiological Response during Incremental Exercise Followed by an Extended Bout of Submaximal Exercise on a Cycle Ergometer." Perceptual and Motor Skills 96, no. 2 (April 2003): 653–63. http://dx.doi.org/10.2466/pms.2003.96.2.653.
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The purpose of this study was to examine the relations of ratings of perceived exertion (RPE) of the legs, chest, and overall body with physiological responses (heart rate and oxygen uptake) both during incremental cycling exercise and the recovery stage (submaximal light exercise after total exhaustion). Subjects were 10 healthy university males ages 18 to 23 years ( M age = 20.5 yr., SD= 1.4 yr.) who performed incremental cycling exercise until exhaustion after 1-min. rest and unloaded cycling for 2 min. They then continued to exercise at a constant load of 30 Watts (used for cooling down; recovery stage) for a total of 25 min. Oxygen uptake and heart rate were measured, and three types of RPE were done; Respiratory (chest; RPE-R), Peripheral (legs; RPE-P), and Overall (overall body; RPE-O) during the exercise and recovery stage. All variables during exercise and RPE-R and RPE-P during recovery stage showed significant linear changes. RPE-O and physiological exercise intensity (oxygen uptake and heart rate) in the recovery stage showed significant curvilinear changes (quadratic). RPE-P were significantly higher than RPE-R both during exercise and the recovery stage and the variables highly correlated ( r ≥.88, p <.05). At the point of exhaustion, RPE-P and RPE-O almost reached a peak, but RPE-R did not. In the exercise period until exhaustion, the regression coefficient of RPE-R (.38) was significantly lower than that of RPE-P (.56) and RPE-O (.50), and RPE-R increased according to an increase of the incremental load, but the amount was significantly lower than those of RPE-P and RPE-O. In the recovery stage after exhaustion, the regression coefficient of RPE-O (−1.35) was significantly greater than that of RPE-P (−1.07). A decrease in RPE-O corresponded to a decrease in heart rate and oxygen uptake, but RPE-P did not, and the recovery of RPE-P tended to be late. The results suggest that relations for the physiological responses of heart rate, oxygen uptake, and RPE, and between each RPE in the recovery stage differed from those during exercise until exhaustion.
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Duncan, Michael J., Mark Lyons, and Joanne Hankey. "Placebo Effects of Caffeine on Short-Term Resistance Exercise to Failure." International Journal of Sports Physiology and Performance 4, no. 2 (June 2009): 244–53. http://dx.doi.org/10.1123/ijspp.4.2.244.
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Purpose:This study examined the placebo effect of caffeine on number of repetitions (reps), rating of perceived exertion (RPE), blood pressure (BP), and peak heart rate (PHR) during resistance-training exercise with repetitions (reps) performed to volitional failure.Methods:Following determination of 1-rep maximum in single-leg leg extension, 15 males performed reps to failure at 60% 1-RM in 3 conditions: control, perceived caffeine condition, and perceived placebo condition presented in a randomized order. Participants were informed they would ingest 250 mL of solution that contained either 3 mg·kg−1 caffeine or 3 mg·kg−1 placebo 1 h before each exercise trial. A deceptive protocol was employed and subjects consumed a placebo solution in both conditions. During each condition, total reps, RPE for the active muscle and overall body, and PHR were recorded.Results:Subjects completed 2 more reps when they perceived they had ingested caffeine. RPE was significantly (P = .04) lower in the perceived caffeine and control conditions and RPE for the active muscle was significantly higher across all conditions compared with RPE for the overall body. No substantial differences were evident in PHR across conditions.Conclusions:Results of this study are similar to studies of actual caffeine ingestion. However, the perception of consuming a substance that purportedly enhances performance is sufficient enough to enable individuals to complete a greater number of reps to failure during short-term resistance exercise.
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Xu, Hao-Jue, Ting Zou, and Zheng-Qin Yin. "Development-related mitochondrial properties of retinal pigment epithelium cells derived from hEROs." International Journal of Ophthalmology 14, no. 8 (August 18, 2021): 1138–50. http://dx.doi.org/10.18240/ijo.2021.08.02.
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AIM: To explore the temporal mitochondrial characteristics of retinal pigment epithelium (RPE) cells obtained from human embryonic stem cells (hESC)-derived retinal organoids (hEROs-RPE), to verify the optimal period for using hEROs-RPE as donor cells from the aspect of mitochondria and to optimize RPE cell-based therapeutic strategies for age-related macular degeneration (AMD). METHODS: RPE cells were obtained from hEROs and from spontaneous differentiation (SD-RPE). The mitochondrial characteristics were analyzed every 20d from day 60 to 160. Mitochondrial quantity was measured by MitoTracker Green staining. Transmission electron microscopy (TEM) was adopted to assess the morphological features of the mitochondria, including their distribution, length, and cristae. Mitochondrial membrane potentials (MMPs) were determined by JC-1 staining and evaluated by flow cytometry, reactive oxygen species (ROS) levels were evaluated by flow cytometry, and adenosine triphosphate (ATP) levels were measured by a luminometer. Differences between two groups were analyzed by the independent-samples t-test, and comparisons among multiple groups were made using one-way ANOVA or Kruskal-Wallis H test when equal variance was not assumed. RESULTS: hEROs-RPE and SD-RPE cells from day 60 to 160 were successfully differentiated from hESCs and expressed RPE markers (Pax6, MITF, Bestrophin-1, RPE65, Cralbp). RPE features, including a cobblestone-like morphology with tight junctions (ZO-1), pigments and microvilli, were also observed in both hEROs-RPE and SD-RPE cells. The mitochondrial quantities of hEROs-RPE and SD-RPE cells both peaked at day 80. However, the cristae of hEROs-RPE mitochondria were less mature and abundant than those of SD-RPE mitochondria at day 80, with hEROs-RPE mitochondria becoming mature at day 100. Both hEROs-RPE and SD-RPE cells showed low ROS levels from day 100 to 140 and maintained a normal MMP during this period. However, hEROs-RPE mitochondria maintained a longer time to produce high levels of ATP (from day 120 to 140) than SD-RPE cells (only day 120). CONCLUSION: hEROs-RPE mitochondria develop more slowly and maintain a longer time to supply high-level energy than SD-RPE mitochondria. From the mitochondrial perspective, hEROs-RPE cells from day 100 to 140 are an optimal cell source for treating AMD.
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Keeling, Eloise, David S. Chatelet, Nicole Y. T. Tan, Farihah Khan, Rhys Richards, Thibana Thisainathan, Patricia Goggin, et al. "3D-Reconstructed Retinal Pigment Epithelial Cells Provide Insights into the Anatomy of the Outer Retina." International Journal of Molecular Sciences 21, no. 21 (November 9, 2020): 8408. http://dx.doi.org/10.3390/ijms21218408.
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The retinal pigment epithelium (RPE) is located between the neuroretina and the choroid, and plays a critical role in vision. RPE cells internalise outer segments (OS) from overlying photoreceptors in the daily photoreceptor renewal. Changes to RPE structure are linked with age and retinopathy, which has been described in the past by conventional 2D electron microscopy. We used serial block face scanning electron microscopy (SBF-SEM) to reconstruct RPE cells from the central mouse retina. Three-dimensional-reconstructed OS revealed the RPE to support large numbers of photoreceptors (90–216 per RPE cell). Larger bi-nucleate RPE maintained more photoreceptors, although their cytoplasmic volume was comparable to smaller mono-nucleate RPE supporting fewer photoreceptors. Scrutiny of RPE microvilli and interdigitating OS revealed the angle and surface area of contact between RPE and photoreceptors. Bi-nucleate RPE contained more mitochondria compared to mono-nucleate RPE. Furthermore, bi-nucleate cells contained larger sub-RPE spaces, supporting a likely association with disease. Use of perfusion-fixed tissues ensured the highest possible standard of preservation, providing novel insights into the 3D RPE architecture and changes linked with retinopathy. This study serves as a benchmark for comparing retinal tissues from donor eyes with age-related macular degeneration (AMD) and other retinopathies.
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Westenskow, Peter D., Felicitas Bucher, Stephen Bravo, Toshihide Kurihara, Daniel Feitelberg, Liliana P. Paris, Edith Aguilar, Jonathan H. Lin, and Martin Friedlander. "iPSC-Derived Retinal Pigment Epithelium Allografts Do Not Elicit Detrimental Effects in Rats: A Follow-Up Study." Stem Cells International 2016 (2016): 1–8. http://dx.doi.org/10.1155/2016/8470263.
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Phototransduction is accomplished in the retina by photoreceptor neurons and retinal pigment epithelium (RPE) cells. Photoreceptors rely heavily on the RPE, and death or dysfunction of RPE is characteristic of age-related macular degeneration (AMD), a very common neurodegenerative disease for which no cure exists. RPE replacement is a promising therapeutic intervention for AMD, and large numbers of RPE cells can be generated from pluripotent stem cells. However, questions persist regarding iPSC-derived RPE (iPS-RPE) viability, immunogenicity, and tumorigenesis potential. We showed previously that iPS-RPE prevent photoreceptor atrophy in dystrophic rats up until 24 weeks after implantation. In this follow-up study, we longitudinally monitored thesame implanted iPS-RPE, in the same animals. We observed no gross abnormalities in the eyes, livers, spleens, brains, and blood in aging rats with iPSC-RPE grafts. iPS-RPE cells that integrated into the subretinal space outlived the photoreceptors and survived for as long as 2 1/2 years while nonintegrating RPE cells were ingested by host macrophages. Both populations could be distinguished using immunohistochemistry and electron microscopy. iPSC-RPE could be isolated from the grafts and maintained in culture; these cells also phagocytosed isolated photoreceptor outer segments. We conclude that iPS-RPE grafts remain viable and do not induce any obvious associated pathological changes.
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Kindzelskii, Andrei L., Victor M. Elner, Susan G. Elner, Dongli Yang, Bret A. Hughes, and Howard R. Petty. "Toll-Like Receptor 4 (TLR4) of Retinal Pigment Epithelial Cells Participates in Transmembrane Signaling in Response to Photoreceptor Outer Segments." Journal of General Physiology 124, no. 2 (July 26, 2004): 139–49. http://dx.doi.org/10.1085/jgp.200409062.
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Retinal pigment epithelial (RPE) cells mediate the recognition and clearance of effete photoreceptor outer segments (POS), a process central to the maintenance of normal vision. Given the emerging importance of Toll-like receptors (TLRs) in transmembrane signaling in response to invading pathogens as well as endogenous substances, we hypothesized that TLRs are associated with RPE cell management of POS. TLR4 clusters on human RPE cells in response to human, but not bovine, POS. However, TLR4 clustering could be inhibited by saturating concentrations of an inhibitory anti-TLR4 mAb. Furthermore, human POS binding to human RPE cells elicited transmembrane metabolic and calcium signals within RPE cells, which could be blocked by saturating doses of an inhibitory anti-TLR4 mAb. However, the heterologous combination of bovine POS and human RPE did not trigger these signals. The pattern recognition receptor CD36 collected at the POS–RPE cell interface for both homologous and heterologous samples, but human TLR4 only collected at the human POS–human RPE cell interface. Kinetic experiments of human POS binding to human RPE cells revealed that CD36 arrives at the POS–RPE interface followed by TLR4 accumulation within 2 min. Metabolic and calcium signals immediately follow. Similarly, the production of reactive oxygen metabolites (ROMs) was observed for the homologous human system, but not the heterologous bovine POS–human RPE cell system. As (a) the bovine POS/human RPE combination did not elicit TLR4 accumulation, RPE signaling, or ROM release, (b) TLR4 arrives at the POS–RPE cell interface just before signaling, (c) TLR4 blockade with an inhibitory anti-TLR4 mAb inhibited TLR4 clustering, signaling, and ROM release in the human POS–human RPE system, and (d) TLR4 demonstrates similar clustering and signaling responses to POS in confluent RPE monolayers, we suggest that TLR4 of RPE cells participates in transmembrane signaling events that contribute to the management of human POS.
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DeVera, Christopher, Jendayi Dixon, Micah A. Chrenek, Kenkichi Baba, Yun Z. Le, P. Michael Iuvone, and Gianluca Tosini. "The Circadian Clock in the Retinal Pigment Epithelium Controls the Diurnal Rhythm of Phagocytic Activity." International Journal of Molecular Sciences 23, no. 10 (May 10, 2022): 5302. http://dx.doi.org/10.3390/ijms23105302.
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The diurnal peak of phagocytosis by the retinal pigment epithelium (RPE) of photoreceptor outer segments (POS) is under circadian control and believed that this process involves interactions from the retina and RPE. Previous studies have demonstrated that a functional circadian clock exists within multiple retinal cell types and RPE. Thereby, the aim of this study was to determine whether the clock in the retina or RPE controls the diurnal phagocytic peak and whether disruption of the circadian clock in the RPE would affect cellular function and the viability during aging. To that, we generated and validated an RPE tissue-specific KO of the essential clock gene, Bmal1, and then determined the daily rhythm in phagocytic activity by the RPE in mice lacking a functional circadian clock in the retina or RPE. Then, using electroretinography, spectral domain-optical coherence tomography, and optomotor response of visual function we determined the effect of Bmal1 removal in young (6 months) and old (18 months) mice. RPE morphology and lipofuscin accumulation was determined in young and old mice. Our data shows that the clock in the RPE, rather than the retina clock, controls the diurnal phagocytic peak. Surprisingly, absence of a functional RPE clock and phagocytic peak does not result in any detectable age-related degenerative phenotype in the retina or RPE. Thus, our results demonstrate that the circadian clock in the RPE controls the daily peak of phagocytic activity. However, the absence of the clock in the RPE does not result in deterioration of photoreceptors or the RPE during aging.
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Arney, Blaine E., Reese Glover, Andrea Fusco, Cristina Cortis, Jos J. de Koning, Teun van Erp, Salvador Jaime, Richard P. Mikat, John P. Porcari, and Carl Foster. "Comparison Of RPE Rating Scales For Session RPE." Medicine & Science in Sports & Exercise 51, Supplement (June 2019): 920–21. http://dx.doi.org/10.1249/01.mss.0000563258.44197.66.
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Smith, Dr Nathan, Dr Olivier Girard, Associate Professor Brendan Scott, and Professor Jeremiah Peiffer. "PRESCRIBING BLOOD FLOW-RESTRICTED CYCLING USING RPE BALANCES THE PHYSIOLOGICAL AND PERCEPTUAL DEMANDS IN HEALTHY ADULTS." Journal of Clinical Exercise Physiology 13, s2 (May 1, 2024): 341. http://dx.doi.org/10.31189/2165-7629-13-s2.341.
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INTRODUCTION Aerobic exercise is commonly prescribed using fixed heart rates or power/speed. These methods may not be suitable when incorporating blood flow restriction (BFR), as this technique can influence these measurements. Prescribing exercise via perception of exertion (RPE), which reflects overall psychophysiological stress, may present an alternative to overcome these issues. Aim: Describe physiological and perceptual responses during fixed-power and fixed-RPE cycling performed with blood flow restriction (BFR_{PWR} and BFR_{RPE}) and without (CON_{PWR} and CON_{RPE}). METHODS Following baseline testing, twelve active males cycled for ten minutes under four conditions. CON_{PWR} was performed first, then the remaining conditions in a randomised and counterbalanced order. BFR_{PWR} and CON_{PWR} were performed at the power equivalent to the first ventilatory threshold (161±38W). CON_{RPE} and BFR_{RPE} were prescribed at the RPE reported during CON_{PWR}. Continuous ventilatory and heart rate measurements were recorded as two-minute averages. Subjective RPE, effort, muscular discomfort, and cuff pain were recorded every two minutes. Blood lactate was measured pre-exercise, post-exercise, and two-minutes post-exercise. RESULTS BFR_{PWR} resulted in the greatest physiological and perceptual responses among all conditions. Power output was lower during BFR_{RPE} (119±48W) than CON_{RPE} (139±47W). Oxygen consumption during BFR_{RPE} (20.8±5.1mL·kg-1·min-1) was lower than CON_{PWR} (25.3±6.0mL·kg-1·min-1, p<0.001) and CON_{RPE} (22.3±5.9mL·kg-1·min-1, p=0.007). Heart rate during CON_{PWR} (143±22beats·min-1) was greater than BFR_{RPE} (133±26beats·min-1, p<0.001) and CON_{RPE} (131±25beats·min-1, p<0.001). Muscular discomfort was not different between BFR_{RPE} (2.5±1.3au) and CON_{PWR}(2.3±1.5au), yet both were greater than CON_{RPE} (p<0.001, 1.8±1.5au). Cuff pain was greater during BFR_{PWR} (3.3±1.7au) than BFR_{RPE} (2.2±1.1au, p<0001). Blood lactate was greater during fixed-power (4.9±3.5mmol·L-1) compared to fixed-RPE trials (3.6±2.7mmol·L-1, p<0.001). CONCLUSIONS BFR_{RPE} caused less discomfort and pain than BFR_{PWR} without compromising physiological stress compared to CON_{RPE}. BFR_{RPE} should be considered when high mechanical loads are contraindicated, or discomfort/pain is undesirable. These findings improve our understanding of aerobic BFR exercise prescription to healthy adults.
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Afanasyeva, M. A., and A. G. Kurguzova. "Comparative analysis of avascular retinal pigment epithelium detachments." Modern technologies in ophtalmology, no. 2 (May 29, 2023): 254–58. http://dx.doi.org/10.25276/2312-4911-2023-2-254-258.
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Purpose. To study anatomical and functional parameters using optical coherence tomography in patients with avascular retinal pigment epithelium (RPE) detachment with age-related macular degeneration (AMD) and central serous chorioretinopathy (CSCR). Material and methods. 40 people with AMD and CSR were examined. Patients were divided depending on the type of RPE detachment: druzenoid – 10 patients, serous RPE detachment in AMD – 20 patients, serous RPE detachment in CSCR – 10 patients. Results. A comparative analysis revealed that serous avascular RPE detachment in AMD is characterized by the greatest height and width in relation to drusenoid RPE detachment and RPE detachment in CSCR. Avascular RPE detachment in CSCR are characterized by the smallest dimensions – both in height and width in relation to other avascular RPE detachments, and the greatest thickness of the choroid in relation to serous RPE detachment in AMD (p = 0.018). Conclusions. The identified features of avascular RPE detachment in AMD and CSCR allow us to choose an adequate tactics for managing patients. Key words: retinal pigment epithelium detachment, age-related macular degeneration, central serous chorioretinopathy
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Yang, Xue, Jin-Yong Chung, Usha Rai, and Noriko Esumi. "SIRT6 overexpression in the nucleus protects mouse retinal pigment epithelium from oxidative stress." Life Science Alliance 6, no. 7 (April 25, 2023): e202201448. http://dx.doi.org/10.26508/lsa.202201448.
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Retinal pigment epithelium (RPE) is essential for the survival of retinal photoreceptors. To study retinal degeneration, sodium iodate (NaIO3) has been used to cause oxidative stress-induced RPE death followed by photoreceptor degeneration. However, analyses of RPE damage itself are still limited. Here, we characterized NaIO3-induced RPE damage, which was divided into three regions: periphery with normal-shaped RPE, transitional zone with elongated cells, and center with severely damaged or lost RPE. Elongated cells in the transitional zone exhibited molecular characteristics of epithelial–mesenchymal transition. Central RPE was more susceptible to stresses than peripheral RPE. Under stresses, SIRT6, an NAD+-dependent protein deacylase, rapidly translocated from the nucleus to the cytoplasm and colocalized with stress granule factor G3BP1, leading to nuclear SIRT6 depletion. To overcome this SIRT6 depletion, SIRT6 overexpression was induced in the nucleus in transgenic mice, which protected RPE from NaIO3and partially preserved catalase expression. These results demonstrate topological differences of mouse RPE and warrant further exploring SIRT6 as a potential target for protecting RPE from oxidative stress-induced damage.
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Leach, Lyndsay L., Nicholas J. Hanovice, Stephanie M. George, Ana E. Gabriel, and Jeffrey M. Gross. "The immune response is a critical regulator of zebrafish retinal pigment epithelium regeneration." Proceedings of the National Academy of Sciences 118, no. 21 (May 18, 2021): e2017198118. http://dx.doi.org/10.1073/pnas.2017198118.
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Loss of the retinal pigment epithelium (RPE) because of dysfunction or disease can lead to blindness in humans. Harnessing the intrinsic ability of the RPE to self-repair is an attractive therapeutic strategy; however, mammalian RPE is limited in its regenerative capacity. Zebrafish possess tremendous intrinsic regenerative potential in ocular tissues, including the RPE, but little is known about the mechanisms driving RPE regeneration. Here, utilizing transgenic and mutant zebrafish lines, pharmacological manipulations, transcriptomics, and imaging analyses, we identified elements of the immune response as critical mediators of intrinsic RPE regeneration. After genetic ablation, the RPE express immune-related genes, including leukocyte recruitment factors such as interleukin 34. We demonstrate that macrophage/microglia cells are responsive to RPE damage and that their function is required for the timely progression of the regenerative response. These data identify the molecular and cellular underpinnings of RPE regeneration and hold significant potential for translational approaches aimed toward promoting a pro-regenerative environment in mammalian RPE.
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Bannister, James W., and Harry A. Newman. "Analysis of Corporate Disclosures on Relative Performance Evaluation." Accounting Horizons 17, no. 3 (September 1, 2003): 235–46. http://dx.doi.org/10.2308/acch.2003.17.3.235.
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The relative performance evaluation (RPE) hypothesis states that firms benefit from comparing their own performance to that of a peer group when evaluating the CEO's performance. Although in theory firms should be employing relative performance to evaluate the CEO, indirect empirical tests in the 1980s and 1990s generally fail to support the RPE hypothesis. This paper examines RPE-related disclosures found in the compensation committee reports provided in proxy statements to determine whether firms actually employ RPE, and to offer insight into why indirect tests generally fail to support the RPE hypothesis. We find that firms do use RPE in determining executive compensation, thus supporting the RPE hypothesis, although RPE usage is not widespread. We also find that several key assumptions underlying prior indirect tests are misspecified for many firms, helping to explain the difficulty in detecting RPE in random samples of firms and suggesting improvements to methodologies employing indirect tests for RPE. Our results also beg the question of why some firms use RPE while other firms do not. We find that RPE usage is positively related to greater monitoring and stakeholder concern about pay and performance, but that performance and CEO power and insulation from pressure do not explain cross-sectional variation in RPE usage. We also examine disclosures related to peer groups and adverse performance-related events since they indirectly relate to RPE and find that many firms filter out negative-performance-related events, but not positive ones. This is equivalent to using one-sided RPE, where a firm excuses the CEO from factors that affect industry performance adversely, but credits the CEO for factors that aid industry performance.
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Gong, Guojin, Laura Yue Li, and Jae Yong Shin. "Relative Performance Evaluation and Related Peer Groups in Executive Compensation Contracts." Accounting Review 86, no. 3 (May 1, 2011): 1007–43. http://dx.doi.org/10.2308/accr.00000042.
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ABSTRACT: This study examines the explicit use of relative performance evaluation (RPE) in executive compensation contracts and the selection of RPE peers. Using S&P 1500 firms’ first proxy disclosures under the SEC’s 2006 executive compensation disclosure rules, we find that about 25 percent of our sample firms explicitly use RPE in setting executive compensation. We demonstrate that a lack of knowledge of both actual peer-group composition and the link between RPE-based performance targets and future peer performance significantly hinder the traditional implicit test from detecting RPE use. We also find that firms consider both costs and benefits of RPE as an incentive mechanism when deciding to use RPE. Finally, both efficient contracting and rent extraction considerations influence RPE peer selection, with the relative importance of these competing considerations depending on RPE firms’ performance.
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Lu, Fangfang, Lyndsay L. Leach, and Jeffrey M. Gross. "mTOR activity is essential for retinal pigment epithelium regeneration in zebrafish." PLOS Genetics 18, no. 3 (March 10, 2022): e1009628. http://dx.doi.org/10.1371/journal.pgen.1009628.
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The retinal pigment epithelium (RPE) plays numerous critical roles in maintaining vision and this is underscored by the prevalence of degenerative blinding diseases like age-related macular degeneration (AMD), in which visual impairment is caused by progressive loss of RPE cells. In contrast to mammals, zebrafish possess the ability to intrinsically regenerate a functional RPE layer after severe injury. The molecular underpinnings of this regenerative process remain largely unknown yet hold tremendous potential for developing treatment strategies to stimulate endogenous regeneration in the human eye. In this study, we demonstrate that the mTOR pathway is activated in RPE cells post-genetic ablation. Pharmacological and genetic inhibition of mTOR activity impaired RPE regeneration, while mTOR activation enhanced RPE recovery post-injury, demonstrating that mTOR activity is essential for RPE regeneration in zebrafish. RNA-seq of RPE isolated from mTOR-inhibited larvae identified a number of genes and pathways dependent on mTOR activity at early and late stages of regeneration; amongst these were components of the immune system, which is emerging as a key regulator of regenerative responses across various tissue and model systems. Our results identify crosstalk between macrophages/microglia and the RPE, wherein mTOR activity is required for recruitment of macrophages/microglia to the RPE injury site. Macrophages/microglia then reinforce mTOR activity in regenerating RPE cells. Interestingly, the function of macrophages/microglia in maintaining mTOR activity in the RPE appeared to be inflammation-independent. Taken together, these data identify mTOR activity as a key regulator of RPE regeneration and link the mTOR pathway to immune responses in facilitating RPE regeneration.
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Shang, Peng, Nadezda A. Stepicheva, Haitao Liu, Olivia Chowdhury, Jonathan Franks, Ming Sun, Stacey Hose, et al. "A Novel Method of Mouse RPE Explant Culture and Effective Introduction of Transgenes Using Adenoviral Transduction for In Vitro Studies in AMD." International Journal of Molecular Sciences 22, no. 21 (November 5, 2021): 11979. http://dx.doi.org/10.3390/ijms222111979.
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Degeneration of retinal pigment epithelium (RPE) is one of the most critical phenotypic changes of age-related macular degeneration (AMD), the leading cause of vision loss in the elderly. While cultured polarized RPE cells with original properties are valuable in in vitro models to study RPE biology and the consequences of genetic and/or pharmacological manipulations, the procedure to establish mouse primary PRE cell culture or pluripotent stem cell-derived RPE cells is time-consuming and yields a limited number of cells. Thus, establishing a mouse in situ RPE culture system is highly desirable. Here we describe a novel and efficient method for RPE explant culture that allows for obtaining biologically relevant RPE cells in situ. These RPE explants (herein referred to as RPE flatmounts) are viable in culture for at least 7 days, can be efficiently transduced with adenoviral constructs, and/or treated with a variety of drugs/chemicals followed by downstream analysis of the signaling pathways/biological processes of interest, such as assessment of the autophagy flux, inflammatory response, and receptor tyrosine kinases stimulation. This method of RPE explant culture is highly beneficial for pharmacological and mechanistic studies in the field of RPE biology and AMD research.
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Green, J. Matt, P. Jason Wickwire, John R. McLester, Shawn Gendle, Geoffrey Hudson, Robert C. Pritchett, and C. Matt Laurent. "Effects of Caffeine on Repetitions to Failure and Ratings of Perceived Exertion During Resistance Training." International Journal of Sports Physiology and Performance 2, no. 3 (September 2007): 250–59. http://dx.doi.org/10.1123/ijspp.2.3.250.
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Context:Ergogenic effects of caffeine on aerobic or endurance exercise are well documented. Conversely, the ergogenic value of caffeine on high-intensity, primarily anaerobic performance is not well understood even though the proposed mechanisms of action for caffeine permit a strong theoretical basis for application to this type of exercise.Purpose:This study examined effects of caffeine (Ca) on number repetitions (reps), ratings of perceived exertion (RPE), and peak heart rate (PHR) during resistance-training exercise with reps performed to volitional failure.Methods:Subjects (N = 17) were tested for 10-rep maximum in bench press (BP) and leg press (LP). In sessions 2 and 3, Ca (~6 mg/kg) or placebo (Pl) was ingested 1 hr beforehand in a double-blind manner and counterbalanced order. Subjects performed 3 sets to failure (BP and LP) with reps, PHR, and RPE recorded each set. Repeated-measures ANOVAs, 2 (trial) × 3 (set), were used to analyze dependent measures with the Tukey honestly significant difference used when necessary as the post hoc test.Results:In BP, no significant differences (Ca vs Pl) were observed (reps, RPE, PHR). During set 3 of LP training, Ca was associated with significantly higher reps (12.5 ± 4.2 vs 9.9 ± 2.6) and PHR (158.5 ± 11.9 vs 151.8 ± 13.2). No signifcant RPE differences were found during LP.Conclusions:The findings of similar RPE concurrent with higher reps suggest that caffeine can blunt pain responses, possibly delaying fatigue in high-intensity resistance training. Ergogenic effects might be limited to the later sets in a resistance-training session. Further research is warranted regarding ergogenic effects of caffeine during resistance training and potential mechanisms of action.
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Durlu, Yusuf K., and Makoto Tamai. "Transplantation of Retinal Pigment Epithelium Using Viable Cryopreserved Cells." Cell Transplantation 6, no. 2 (March 1997): 149–62. http://dx.doi.org/10.1177/096368979700600209.
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Transplantation of retinal pigment epithelium (RPE) may have potential clinical application for the surgical treatment of RPE-specific retinal degeneration, including age-related macular degeneration. The feasibility of an RPE storage bank has been investigated by experimenting with transplantation using viable, cryopreserved RPE cells. Fresh and cultured fetal human and bovine RPE cells were cryopreserved in 90% fetal bovine serum containing 10% dimethyl sulfoxide. The viability of the cells before and after cryopreservation was evaluated by trypan blue dye exclusion test, microculture tetrazolium assay (MTA), tissue culture, and transplantation after cryopreservation. The origin of RPE cells before and after cryopreservation was assessed by immunocytochemistry, immunoblotting, and indirect ELISA of RPE-marker protein using cytokeratin for cultured fetal human RPE cells and by immunocytochemistry of cellular retinaldehyde-binding protein (CR-ALBP) for cultured bovine RPE cells. Freshly isolated and cryopreserved uncultured bovine RPE cells were transplanted by posterior transscleral approach into the subretinal spaces of adult albino rabbits and 23-day-old Royal College of Surgeons (RCS) rats with a 33 gauge Hamilton syringe. Following surgery, artificial retinal blebs were confirmed by fundus examination. Morphologic examination was performed postoperatively by light and electron microscopy in albino rabbits and by light microscopy in RCS rats up to 3 mo. Control subretinal injections using vehicle solution also were performed in RCS rats. Cultured fetal human and bovine RPE cells after cryopreservation were found to be viable, based on the results of trypan blue dye exclusion test, MTA, tissue culture, and transplantation. Expression and reexpression of cytokeratin intermediate filaments in cultured fetal human RPE were demonstrated by immunocytochemistry, immunoblotting, and indirect ELISA before and after cryopreservation. Immunocytochemistry of CRALBP before and after cryopreservation in uncultured bovine RPE cells disclosed expression and reexpression of RPE cell marker protein. No uncultured fetal human RPE cells showed proliferation in tissue culture after cryopreservation. In rabbits, light and electron microscopy disclosed xenografted RPE cells residing on Bruch's membrane of the host retina. No sign of graft vs. host reaction was observed. No morphologic difference was noted between the fresh and 10-day-old cryopreserved RPE cells in situ following transplantation at day 25. In RCS rats, subretinal injection of 3-wk-old cryopreserved bovine RPE cells partially rescued photoreceptor cells locally at the transplanted area observed at 3 mo postoperatively. The retinal photoreceptors at the inferior hemisphere of the transplanted eye and the eye injected with vehicle solution showed no rescue effect. We found that cryopreserved cultured fetal human RPE cells and uncultured and cultured bovine RPE cells can be used for RPE transplantation studies. The ability to create an RPE storage bank as a source of donor cells may result in several clinical advantages.
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Xu, Rong, Brianna K. Ritz, Yekai Wang, Jiancheng Huang, Chen Zhao, Kaizheng Gong, Xinnong Liu, and Jianhai Du. "The retina and retinal pigment epithelium differ in nitrogen metabolism and are metabolically connected." Journal of Biological Chemistry 295, no. 8 (January 17, 2020): 2324–35. http://dx.doi.org/10.1074/jbc.ra119.011727.
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Defects in energy metabolism in either the retina or the immediately adjacent retinal pigment epithelium (RPE) underlie retinal degeneration, but the metabolic dependence between retina and RPE remains unclear. Nitrogen-containing metabolites such as amino acids are essential for energy metabolism. Here, we found that 15N-labeled ammonium is predominantly assimilated into glutamine in both the retina and RPE/choroid ex vivo. [15N]Ammonium tracing in vivo show that, like the brain, the retina can synthesize asparagine from ammonium, but RPE/choroid and the liver cannot. However, unless present at toxic concentrations, ammonium cannot be recycled into glutamate in the retina and RPE/choroid. Tracing with 15N-labeled amino acids show that the retina predominantly uses aspartate transaminase for de novo synthesis of glutamate, glutamine, and aspartate, whereas RPE uses multiple transaminases to utilize and synthesize amino acids. Retina consumes more leucine than RPE, but little leucine is catabolized. The synthesis of serine and glycine is active in RPE but limited in the retina. RPE, but not the retina, uses alanine as mitochondrial substrates through mitochondrial pyruvate carrier. However, when the mitochondrial pyruvate carrier is inhibited, alanine may directly enter the retinal mitochondria but not those of RPE. In conclusion, our results demonstrate that the retina and RPE differ in nitrogen metabolism and highlight that the RPE supports retinal metabolism through active amino acid metabolism.
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Nagata, Junya, Satomi Shiose, Keijiro Ishikawa, Takuma Fukui, Kumiko Kano, Kenichiro Mori, Takahito Nakama, Shoji Notomi, and Koh-Hei Sonoda. "Clinical Characteristics of Eyes with Neovascular Age-Related Macular Degeneration and Retinal Pigment Epithelium Tears." Journal of Clinical Medicine 12, no. 17 (August 24, 2023): 5496. http://dx.doi.org/10.3390/jcm12175496.
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Background: Although anti-vascular endothelial growth factor (anti-VEGF) therapy is the first choice of treatment for eyes with neovascular age-related macular degeneration (AMD), it sometimes results in retinal pigment epithelium (RPE) tears. This study presents the detailed clinical characteristics of RPE tears to help predict their occurrence before anti-VEGF therapy initiation. Methods: This study retrospectively analyzed neovascular age-related macular degeneration (nAMD) patients who visited the Kyushu University Hospital and started anti-VEGF therapy between April 2013 and June 2020. Using medical records, we collected the clinical data of patients with RPE tears, including age, sex, best-corrected visual acuity (BCVA), number of anti-VEGF drug injections and the type and size of pigment epithelial detachment (PED). Results: RPE tears occurred in 16 (1.50%) eyes of 16 patients in all 1068 nAMD eyes of 987 patients. The mean age of these patients with RPE tear was 81.7 ± 8.7 years. Fifteen eyes had typical AMD and one eye had polypoidal choroidal vasculopathy. The mean number of anti-VEGF drug injections before RPE tears was 5.0 ± 5.1. All patients experienced PED before the RPE tear (hemorrhagic, 4 eyes; serous vascular, 2 eyes; fibrovascular, 10 eyes). The average PED height and area were 615.7 ± 175.3 μm and 21.0 ± 7.2 mm2, respectively. The sub-RPE cleft was observed in 10 eyes. The logMAR BCVA immediately after the RPE tear (0.73 ± 0.40) at 6 months (0.86 ± 0.51) and 12 months (0.84 ± 0.43) after the RPE tear were significantly worse than that before the RPE tear (0.58 ± 0.31; p < 0.05). The BCVA of patients with RPE tears that spread to the fovea was poorer than that of patients without RPE tears. Conclusions: In patients with nAMD, RPE tears tended to occur in typical AMD eyes with high or large PEDs, and sub-RPE clefts. The visual prognosis depended on whether the RPE tear included the fovea.
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Maruotti, Julien, Srinivas R. Sripathi, Kapil Bharti, John Fuller, Karl J. Wahlin, Vinod Ranganathan, Valentin M. Sluch, et al. "Small-molecule–directed, efficient generation of retinal pigment epithelium from human pluripotent stem cells." Proceedings of the National Academy of Sciences 112, no. 35 (August 12, 2015): 10950–55. http://dx.doi.org/10.1073/pnas.1422818112.
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Age-related macular degeneration (AMD) is associated with dysfunction and death of retinal pigment epithelial (RPE) cells. Cell-based approaches using RPE-like cells derived from human pluripotent stem cells (hPSCs) are being developed for AMD treatment. However, most efficient RPE differentiation protocols rely on complex, stepwise treatments and addition of growth factors, whereas small-molecule–only approaches developed to date display reduced yields. To identify new compounds that promote RPE differentiation, we developed and performed a high-throughput quantitative PCR screen complemented by a novel orthogonal human induced pluripotent stem cell (hiPSC)-based RPE reporter assay. Chetomin, an inhibitor of hypoxia-inducible factors, was found to strongly increase RPE differentiation; combination with nicotinamide resulted in conversion of over one-half of the differentiating cells into RPE. Single passage of the whole culture yielded a highly pure hPSC-RPE cell population that displayed many of the morphological, molecular, and functional characteristics of native RPE.
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Mao, Yingyu, and Silvia C. Finnemann. "Acute RhoA/Rho Kinase Inhibition Is Sufficient to Restore Phagocytic Capacity to Retinal Pigment Epithelium Lacking the Engulfment Receptor MerTK." Cells 10, no. 8 (July 29, 2021): 1927. http://dx.doi.org/10.3390/cells10081927.
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The diurnal phagocytosis of spent photoreceptor outer segment fragments (POS) by retinal pigment epithelial (RPE) cells is essential for visual function. POS internalization by RPE cells requires the assembly of F-actin phagocytic cups beneath surface-tethered POS and Mer tyrosine kinase (MerTK) signaling. The activation of the Rho family GTPase Rac1 is necessary for phagocytic cup formation, and Rac1 is activated normally in MerTK-deficient RPE. We show here that mutant RPE lacking MerTK and wild-type RPE deprived of MerTK ligand both fail to form phagocytic cups regardless of Rac1 activation. However, in wild-type RPE in vivo, a decrease in RhoA activity coincides with the daily phagocytosis burst, while RhoA activity in MerTK-deficient RPE is constant. Elevating RhoA activity blocks phagocytic cup formation and phagocytosis by wild-type RPE. Conversely, inhibiting RhoA effector Rho kinases (ROCKs) rescues both F-actin assembly and POS internalization of primary RPE if MerTK or its ligand are lacking. Most strikingly, acute ROCK inhibition is sufficient to induce the formation and acidification of endogenous POS phagosomes by MerTK-deficient RPE ex vivo. Altogether, RhoA pathway inactivation is a necessary and sufficient downstream effect of MerTK phagocytic signaling such that the acute manipulation of cytosolic ROCK activity suffices to restore phagocytic capacity to MerTK-deficient RPE.
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Mora, Rosalia C., Vera L. Bonilha, Bo-Chul Shin, Jane Hu, Leona Cohen-Gould, Dean Bok, and Enrique Rodriguez-Boulan. "Bipolar assembly of caveolae in retinal pigment epithelium." American Journal of Physiology-Cell Physiology 290, no. 3 (March 2006): C832—C843. http://dx.doi.org/10.1152/ajpcell.00405.2005.
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Caveolae and their associated structural proteins, the caveolins, are specialized plasmalemmal microdomains involved in endocytosis and compartmentalization of cell signaling. We examined the expression and distribution of caveolae and caveolins in retinal pigment epithelium (RPE), which plays key roles in retinal support, visual cycle, and acts as the main barrier between blood and retina. Electron microscopic observation of rat RPE, in situ primary cultures of rat and human RPE and a rat RPE cell line (RPE-J) demonstrated in all cases the presence of caveolae in both apical and basolateral domains of the plasma membrane. Caveolae were rare in RPE in situ but were frequent in primary RPE cultures and in RPE-J cells, which correlated with increased levels in the expression of caveolin-1 and -2. The bipolar distribution of caveolae in RPE is striking, as all other epithelial cells examined to date (liver, kidney, thyroid, and intestinal) assemble caveolae only at the basolateral side. This might be related to the nonpolar distribution of both caveolin-1 and 2 in RPE because caveolin-2 is basolateral and caveolin-1 nonpolar in other epithelial cells. The bipolar localization of plasmalemmal caveolae in RPE cells may reflect specialized roles in signaling and trafficking important for visual function.
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Hellinen, Laura, Heidi Hongisto, Eva Ramsay, Kai Kaarniranta, Kati-Sisko Vellonen, Heli Skottman, and Marika Ruponen. "Drug Flux Across RPE Cell Models: The Hunt for An Appropriate Outer Blood–Retinal Barrier Model for Use in Early Drug Discovery." Pharmaceutics 12, no. 2 (February 19, 2020): 176. http://dx.doi.org/10.3390/pharmaceutics12020176.
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The retinal pigment epithelial (RPE) cell monolayer forms the outer blood–retinal barrier and has a crucial role in ocular pharmacokinetics. Although several RPE cell models are available, there have been no systematic comparisons of their barrier properties with respect to drug permeability. We compared the barrier properties of several RPE secondary cell lines (ARPE19, ARPE19mel, and LEPI) and both primary (hfRPE) and stem-cell derived RPE (hESC-RPE) cells by investigating the permeability of nine drugs (aztreonam, ciprofloxacin, dexamethasone, fluconazole, ganciclovir, ketorolac, methotrexate, voriconazole, and quinidine) across cell monolayers. ARPE19, ARPE19mel, and hfRPE cells displayed a narrow Papp value range, with relatively high permeation rates (5.2–26 × 10−6 cm/s. In contrast, hESC-RPE and LEPI cells efficiently restricted the drug flux, and displayed even lower Papp values than those reported for bovine RPE-choroid, with the range of 0.4–32 cm−6/s (hESC-RPE cells) and 0.4–29 × 10−6 cm/s, (LEPI cells). Therefore, ARPE19, ARPE19mel, and hfRPE cells failed to form a tight barrier, whereas hESC-RPE and LEPI cells restricted the drug flux to a similar extent as bovine RPE-choroid. Therefore, LEPI and hESC-RPE cells are valuable tools in ocular drug discovery.
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Rebustini, Ivan T., Susan E. Crawford, and S. Patricia Becerra. "PEDF Deletion Induces Senescence and Defects in Phagocytosis in the RPE." International Journal of Molecular Sciences 23, no. 14 (July 13, 2022): 7745. http://dx.doi.org/10.3390/ijms23147745.
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The retinal pigment epithelium (RPE) expresses the Serpinf1 gene to produce pigment epithelium-derived factor (PEDF), a retinoprotective protein that is downregulated with cell senescence, aging and retinal degenerations. We determined the expression of senescence-associated genes in the RPE of 3-month-old mice that lack the Serpinf1 gene and found that Serpinf1 deletion induced H2ax for histone H2AX protein, Cdkn1a for p21 protein, and Glb1 gene for β-galactosidase. Senescence-associated β-galactosidase activity increased in the Serpinf1 null RPE when compared with wild-type RPE. We evaluated the subcellular morphology of the RPE and found that ablation of Serpinf1 increased the volume of the nuclei and the nucleoli number of RPE cells, implying chromatin reorganization. Given that the RPE phagocytic function declines with aging, we assessed the expression of the Pnpla2 gene, which is required for the degradation of photoreceptor outer segments by the RPE. We found that both the Pnpla2 gene and its protein PEDF-R declined with the Serpinf1 gene ablation. Moreover, we determined the levels of phagocytosed rhodopsin and lipids in the RPE of the Serpinf1 null mice. The RPE of the Serpinf1 null mice accumulated rhodopsin and lipids compared to littermate controls, implying an association of PEDF deficiency with RPE phagocytosis dysfunction. Our findings establish PEDF loss as a cause of senescence-like changes in the RPE, highlighting PEDF as both a retinoprotective and a regulatory protein of aging-like changes associated with defective degradation of the photoreceptor outer segment in the RPE.
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Schaeffer-Gerschutz, Sarah A., Lynn A. Darby, and Kathy D. Browder. "Differentiated Ratings of Perceived Exertion and Physiological Responses during Aerobic Dance Steps by Impact/Type of Arm Movement." Perceptual and Motor Skills 90, no. 2 (April 2000): 457–71. http://dx.doi.org/10.2466/pms.2000.90.2.457.
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Overall ratings of perceived exertion, i.e., undifferentiated RPE, are often used as indicators of exercise intensity during walking, jogging, and cycling; however, conflicting results concerning RPE during aerobic dance exercise have been reported, and the use of differentiated RPE, i.e., local RPE and central RPE, has not been investigated. The purposes of this study were to assess local, central, and over-all RPE, and physiological responses [heart rate (HR); % HRmax; absolute and relative VO2; % VO2 max, ventilation (VE), ventilatory equivalent (VE · VO2−1); and oxygen pulse] during aerobic dance exercise varied by Arm Movement (Static Arm vs Dynamic Arm) and Impact (High vs Low). Trained women ( N = 25; max VO2 = 50.4± 7.5 ml · kg−1 · min.−1) completed four aerobic dance steps. No RPE were significantly correlated with heart rate or VO2; however, for all steps all RPE were significantly ( r = .40–,62) correlated with VE · VO2−1or VE. No interactions were present for RPE or physiological variables, and main effects were noted for Impact and Arm Movement. All RPE were greater for High Impact and for Static Arm Movement. Because VE and VE · VO2−1 were correlated with Overall RPE for all steps, this may suggest that participants “attended to” perceived changes in respiratory phenomena during aerobic dance exercise. It appears that during combined arm-and-leg aerobic dance exercise the use of Overall RPE is sufficient to assess perceptual sensations associated with the intensity of the exercise. Changes in Overall RPE were proportionate to objective measures of exercise intensity, i.e., HR and VO2; however, it is recommended that both HR and Overall RPE be used to assess fully a participant's objective and subjective responses during aerobic dance exercise.
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Andrade, Carolina Pieroni, Antonio Roberto Zamunér, Meire Forti, Thalita Fonseca de França, and Ester da Silva. "The Borg CR-10 scale is suitable to quantify aerobic exercise intensity in women with fibromyalgia syndrome." Fisioterapia e Pesquisa 24, no. 3 (September 2017): 267–72. http://dx.doi.org/10.1590/1809-2950/16558824032017.
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ABSTRACT Patients with Fibromyalgia syndrome (FMS) report higher ratings of perceived exertion (RPE) compared to healthy individuals for the same exercise intensity; however, to our knowledge, no studies have evaluated RPE at the ventilatory anaerobic threshold (VAT) for this population. This study aimed to assess RPE using the Borg CR-10 scale during a cardiopulmonary exercise test (CPET) in women with FMS. Twenty-four women with FMS and twenty healthy control subjects (HC) voluntarily participated in this study. Near the end of every 1-minute period during CPET, subjects were asked to report their RPE for fatigue in the lower limbs (RPE-L) and dyspnea (RPE-D), respectively, according to the Borg CR-10 scale. FMS subjects showed higher RPE-L and RPE-D compared to HC subjects at free wheel and at the first load increment. However, no significant difference was observed between groups for power output. There was no significant difference between groups for RPE-L and RPE-D reported at VAT and peak CPET. However, FMS subjects showed lower power output compared to HC subjects. The present results showed that FMS subjects present higher RPE compared to HC subjects. However, RPE reported at VAT and at peak CPET was not different between groups. The Borg CR-10 scale scores obtained at VAT can be used as an additional parameter for prescribing exercise intensity in aerobic training protocols for women with FMS.
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Yang, Xue, Usha Rai, Jin-Yong Chung, and Noriko Esumi. "Fine Tuning of an Oxidative Stress Model with Sodium Iodate Revealed Protective Effect of NF-κB Inhibition and Sex-Specific Difference in Susceptibility of the Retinal Pigment Epithelium." Antioxidants 11, no. 1 (December 31, 2021): 103. http://dx.doi.org/10.3390/antiox11010103.
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Oxidative stress of the retinal pigment epithelium (RPE) is a major risk factor for age-related macular degeneration (AMD). As a dry AMD model via oxidative stress, sodium iodate (NaIO3), which is primarily toxic to the RPE, has often been used at a high dose to cause RPE death for studying photoreceptor degeneration. Thus, characterization of RPE damage by a low dose of NaIO3 is still limited. To quantify RPE damage caused by NaIO3 in mice, we recently developed a morphometric method using RPE flat-mounts. Here, we report that NaIO3 has a narrow range of dose–effect correlation at 11–18 mg/kg body weight in male C57BL/6J mice. We evaluated the usefulness of our quantification method in two experimental settings. First, we tested the effect of NF-κB inhibition on NaIO3-induced RPE damage in male C57BL/6J mice. IKKβ inhibitor BAY 651942 suppressed upregulation of NF-κB targets and protected the RPE from oxidative stress. Second, we tested sex-specific differences in NaIO3-induced RPE damage in C57BL/6J mice using a low dose near the threshold. NaIO3 caused more severe RPE damage in female mice than in male mice. These results demonstrate the usefulness of the quantification method and the importance of fine-tuning of the NaIO3 dose. The results also show the therapeutic potential of IKKβ inhibition for oxidative stress-related RPE diseases, and reveal previously-unrecognized sex-specific differences in RPE susceptibility to oxidative stress.
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Piancino, Maria Grazia, Francesco MacDonald, Ivana Laponte, Rosangela Cannavale, Vito Crincoli, and Paola Dalmasso. "Juvenile/Adolescent Idiopatic Scoliosis and Rapid Palatal Expansion. A Pilot Study." Children 8, no. 5 (April 30, 2021): 362. http://dx.doi.org/10.3390/children8050362.
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The question of whether orthodontic therapy by means of rapid palatal expansion (RPE) affects the spine during development is important in clinical practice. RPE is an expansive, fixed therapy conducted with heavy forces to separate the midpalatal suture at a rate of 0.2–0.5 mm/day. The aim of the study was to evaluate the influence of RPE on the curves of the spine of juvenile/adolescent idiopathic scoliosis patients. Eighteen patients under orthopedic supervision for juvenile/adolescent idiopathic scoliosis and independently treated with RPE for orthodontic reasons were included in the study: Group A, 10 subjects (10.4 ± 1.3 years), first spinal radiograph before the application of the RPE, second one during the orthodontic therapy with RPE; Group B, 8 patients (11.3 ± 1.6 years), first radiograph during the use of RPE second one after the removal. Group A showed a significant worsening of the Cobb angle (p ≤ 0.005) at the second radiograph after RPE. Group B showed a significant improvement of the Cobb angle (p = 0.01) at the second radiograph after removal of RPE. Based on the results, the use of RPE during adolescence might influence the spinal curves of patients with idiopathic scoliosis.
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Sanada, Takayuki Jujo, Nobuhiro Tanabe, Hatsue Ishibashi-Ueda, Keiichi Ishida, Akira Naito, Seiichiro Sakao, Rika Suda, et al. "Involvement of pulmonary arteriopathy in the development and severity of reperfusion pulmonary edema after pulmonary endarterectomy." Pulmonary Circulation 9, no. 2 (April 2019): 204589401984643. http://dx.doi.org/10.1177/2045894019846439.
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Reperfusion pulmonary edema (RPE) is a common complication after pulmonary endarterectomy (PEA) in patients with chronic thromboembolic pulmonary hypertension (CTEPH). However, the precise mechanisms underlying the development of RPE remain unclear. To evaluate the effects of pulmonary vasculopathy on RPE, the severity of the pulmonary arteriopathies and venopathies of lung tissues biopsied during PEA were pathologically quantified in 33 CTEPH patients. The severity of RPE was classified from grade 0 (no RPE) to 4 (death due to RPE) based on the arterial oxygen tension/inspiratory oxygen fraction (P/F ratio) and necessity of respiratory management. Among the 33 patients (27 women; mean age = 63.3 years), 17 (51.5%) patients developed RPE. The severity of pulmonary arteriopathy (obstruction ratio) correlated with the grade of RPE (r = 0.576, P = 0.0005). The obstruction ratio also correlated with the P/F ratio (r = −0.543, P = 0.001) and the perioperative mean pulmonary arterial pressure (r = 0.445, P = 0.009). Multivariate logistic regression analysis revealed that the obstruction ratio was a significant independent determinant for the development of RPE (odds ratio = 15.7; 95% confidence interval = 2.29–108.00, P = 0.005). In conclusion, pulmonary arteriopathy could be a determinant of the development and severity of RPE after PEA.
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Rutkowski, Jason J., Robert J. Robertson, Wayland D. Tseh, Jennifer L. Caputo, Daniel J. Keefer, Kristin M. Sutika, and Donald W. Morgan. "Assessment of RPE Signal Dominance at Slow to Moderate Walking Speeds in Children." Pediatric Exercise Science 16, no. 4 (November 2004): 334–42. http://dx.doi.org/10.1123/pes.16.4.334.
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The purpose of this investigation was to determine whether either the differentiated ratings of perceived exertion (RPE) for the legs (RPE-L) or chest (RPE-C) were higher than the overall body RPE (RPE-O) in children performing treadmill walking. A differentiated RPE that was higher than the RPE-O was considered the dominant perceptual signal. Thirty-one 10-year-old participants (16 boys, 15 girls) performed six separate 5-min bouts of level treadmill walking at different speeds. During each bout of exercise, RPEs were recorded using the modified Children’s OMNI Scale. Oxygen consumption (VO2), heart rate (HR), and ventilation (VE) were measured during Minutes 4 and 5 at each walking speed. VO2, HR, and VE increased as walking speed increased, as did perceived exertion. No differences were observed among RPE-O, RPE-L, and RPE-C at any speed. In addition, boys and girls exhibited similar responses for each perceptual and physiological variable. In conclusion, a dominant differentiated perceptual rating was not found at slow-to-moderate treadmill walking speeds for either boys or girls. Neither the respiratory–metabolic nor peripheral ratings of perceived exertion appeared to dominate the whole-body sensory-integration process in this sample.
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Campos Váquez, Miguel Ángel, and Francisco Javier Toscano Belanda. "Comparación de la percepción subjetiva del esfuerzo entre partidos amistosos y diferentes tipos de sesión en futbolistas profesionales (Comparison of perceived exertion in friendly matches and different types of training sessions in professional soccer p." Retos, no. 34 (November 2, 2017): 66–70. http://dx.doi.org/10.47197/retos.v0i34.55248.
Full textAbstract:
El objetivo de la investigación fue comparar la percepción subjetiva del esfuerzo (RPE) y la carga derivada de ella (RPE-TL) durante partidos amistosos (PA) con una participación de 45 minutos por jugador (PA.45) o superior a 65 minutos (PA+65), y diferentes tipos de sesión de entrenamiento: condición física (CF), táctica (TAC) y activación pre-partido (ACTV), en jugadores profesionales de fútbol. 12 futbolistas pertenecientes al mismo equipo (1ª división española) participaron en este estudio. La RPE fue registrada tras cada sesión de entrenamiento y PA, cuantificándose posteriormente la carga interna derivada de ella (RPE-TL). Los resultados reflejaron que los PA+65, tuvieron una RPE substancialmente mayor que los PA.45 (7.8 vs 6.8). Además, todos los tipos de sesión reflejaron una RPE y RPE-TL substancialmente inferior a los PA+65. Tan solo las sesiones de CF alcanzaron valores de RPE y RPE-TL superiores a los reflejados en los PA.45 (7.1 vs. 6.8 y 597 vs. 509 unidades arbitrarias respectivamente). Estos resultados nos muestran que las demandas perceptuales de la competición no fueron replicadas en los diferentes tipos de sesiones de entrenamiento analizadas. Por tanto, podría ser necesario aumentar el volumen y/o la exigencia de algunas sesiones de entrenamiento, para someter a los jugadores a una exigencia similar a la de la competición. Abstract. The aim of the study was to compare perception of exertion (RPE) and RPE-derived internal training load between friendly matches (FM) played during 45 minutes (FM.45) or more than 65 minutes (FM+65), and different types of training sessions: fitness (FIT), tactical (TAC) and pre-match activation (ACTV) in professional soccer players. 12 soccer players from the same team (1st Spanish Division) participated in this study. RPE was registered after every training session and FM. Afterward, RPE-derived internal load was calculated (RPE-TL). Results showed that FM+65 obtained a substantially higher RPE than FM.45 (7.8 vs 6.8). Besides, all types of training sessions reflected a substantially lower RPE and RPE-TL than FM+65. Only FIT sessions reached RPE and RPE-TL values higher than those reflected in FM.45 (7.1 vs. 6.8 and 597 vs. 509 arbitrary units respectively). These results show that perceptual demands of competition were not replicated in the different types of training sessions analysed. It may be necessary to increase the volume and/or the exertion of certain training sessions to bring players closer to the demands of competition.
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Nabi, I. R., A. P. Mathews, L. Cohen-Gould, D. Gundersen, and E. Rodriguez-Boulan. "Immortalization of polarized rat retinal pigment epithelium." Journal of Cell Science 104, no. 1 (January 1, 1993): 37–49. http://dx.doi.org/10.1242/jcs.104.1.37.
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Rat retinal pigment epithelial (RPE) cells were immortalized by infection with a temperature-sensitive tsA SV40 virus and following cloning and selection for epithelial properties the polarized RPE-J cell line was obtained. At the permissive temperature of 33 degrees C, RPE-J cells behave as an immortalized cell line. When RPE-J cells are grown on nitrocellulose filters coated with a thin layer of Matrigel in the presence of 10(−8) M retinoic acid for 6 days at 33 degrees C and then switched for 33–36 hours to the non-permissive temperature of 40 degrees C, they acquire a differentiated polarized RPE phenotype. Under these growth conditions, RPE-J cells exhibit circumferential staining for the tight-junction protein ZO-1 and acquire a transepithelial resistance of 350 ohms cm2. Morphologically, RPE-J cells exhibit a characteristic RPE morphology with extensive apical microvilli as well as numerous dense bodies including premelanosomes and varied multilamellar structures. Ruthenium red labeling revealed the frequent basal localization of the tight junction. The cells were identified to be of rat RPE origin by their expression of the rat RPE marker RET-PE2 and their ability to phagocytose latex beads. While RPE-J cells are capable of sorting influenza and vesicular stomatitis virus to the apical and basal surfaces, respectively, the Na,K-ATPase is not polarized and the neural cell adhesion molecule, N-CAM, is localized exclusively to the lateral surface. In vivo the apical surface of RPE interacts with the adjacent neural retina and the Na,K-ATPase and N-CAM are both apical; the altered polarity of these two proteins in RPE-J cells may be a consequence of the absence of apical interaction with the neural retina in culture. Previous studies of RPE have been restricted to the use of primary cultures and the RPE-J cell line should prove an excellent model system for the study of the mechanisms determining the characteristic polarity and functions of the retinal pigment epithelium.
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Park, Sun Young, Woo Chang Song, Beomjin Kim, Jin-Woo Oh, and Geuntae Park. "Nano-Graphene Oxide-Promoted Epithelial–Mesenchymal Transition of Human Retinal Pigment Epithelial Cells through Regulation of Phospholipase D Signaling." Nanomaterials 11, no. 10 (September 28, 2021): 2546. http://dx.doi.org/10.3390/nano11102546.
Full textAbstract:
Nano-graphene oxide (Nano-GO) is an extensively studied multifunctional carbon nanomaterial with attractive applications in biomedicine and biotechnology. However, few studies have been conducted to assess the epithelial-to-mesenchymal transition (EMT) in the retinal pigment epithelium (RPE). We aimed to determine whether Nano-GO induces EMT by regulating phospholipase D (PLD) signaling in human RPE (ARPE-19) cells. The physicochemical characterization of Nano-GO was performed using a Zetasizer, X-ray diffraction, Fourier-transform infrared spectroscopy, and transmission electron microscopy. RPE cell viability assays were performed, and the migratory effects of RPE cells were evaluated. RPE cell collagen gel contraction was also determined. Intracellular reactive oxygen species (ROS) levels were determined by fluorescence microscopy and flow cytometry. Immunofluorescence staining and western blot analysis were used to detect EMT-related protein expression. Phospholipase D (PLD) enzymatic activities were also measured. Nano-GO significantly enhanced the scratch-healing ability of RPE cells, indicating that the RPE cell migration ability was increased. Following Nano-GO treatment, the RPE cell penetration of the chamber was significantly promoted, suggesting that the migratory ability was strengthened. We also observed collagen gel contraction and the generation of intracellular ROS in RPE cells. The results showed that Nano-GO induced collagen gel contraction and intracellular ROS production in RPE cells. Moreover, immunofluorescence staining and western blot analysis revealed that Nano-GO significantly regulated key molecules of EMT, including epithelial-cadherin, neural-cadherin, α-smooth muscle actin, vimentin, and matrix metalloproteinases (MMP-2 and MMP-9). Interestingly, Nano-GO-induced RPE cell migration and intracellular ROS production were abrogated in PLD-knockdown RPE cells, indicating that PLD activation played a crucial role in the Nano-GO-induced RPE EMT process. We demonstrate for the first time that Nano-GO promotes RPE cell migration through PLD-mediated ROS production. We provide preliminary evidence to support the hypothesis that Nano-GO has adverse health effects related to RPE damage.
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Voisin, Audrey, Christelle Monville, Alexandra Plancheron, Emile Béré, Afsaneh Gaillard, and Nicolas Leveziel. "Cathepsin B pH-Dependent Activity Is Involved in Lysosomal Dysregulation in Atrophic Age-Related Macular Degeneration." Oxidative Medicine and Cellular Longevity 2019 (December 6, 2019): 1–15. http://dx.doi.org/10.1155/2019/5637075.
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Age-related macular degeneration (AMD) is characterized by retinal pigment epithelial (RPE) cell dysfunction beginning at early stages of the disease. The lack of an appropriate in vitro model is a major limitation in understanding the mechanisms leading to the occurrence of AMD. This study compared human-induced pluripotent stem cell- (hiPSC-) RPE cells derived from atrophic AMD patients (77 y/o±7) to hiPSC-RPE cells derived from healthy elderly individuals with no drusen or pigmentary alteration (62.5 y/o±17.5). Control and AMD hiPSC-RPE cell lines were characterized by immunofluorescence, flow cytometry, and electronic microscopy. The toxicity level of iron after Fe-NTA treatment was evaluated by an MTT test and by the detection of dichloro-dihydro-fluorescein diacetate. Twelve hiPSC-RPE cell lines (6 AMD and 6 controls) were used for the experiment. Under basal conditions, all hiPSC-RPE cells expressed a phenotypic profile of senescent cells with rounded mitochondria at passage 2. However, the treatment with Fe-NTA induced higher reactive oxygen species production and cell death in hiPSC-RPE AMD cells than in hiPSC-RPE Control cells. Interestingly, functional analysis showed differences in lysosomal activity between the two populations. Indeed, Cathepsin B activity was higher in hiPSC-RPE AMD cells compared to hiPSC-RPE Control cells in basal condition and link to a pH more acidic in this cell population. Moreover, oxidative stress exposure leads to an increase of Cathepsin D immature form levels in both populations, but in a higher proportion in hiPSC-RPE AMD cells. These findings could demonstrate that hiPSC-RPE AMD cells have a typical disease phenotype compared to hiPSC-RPE Control cells.
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Sugita, Sunao, Yoko Futatsugi, Masaaki Ishida, Ayaka Edo, and Masayo Takahashi. "Retinal Pigment Epithelial Cells Derived from Induced Pluripotent Stem (iPS) Cells Suppress or Activate T Cells via Costimulatory Signals." International Journal of Molecular Sciences 21, no. 18 (September 5, 2020): 6507. http://dx.doi.org/10.3390/ijms21186507.
Full textAbstract:
Human retinal pigment epithelial (RPE) cells derived from induced pluripotent stem (iPS) cells have immunosuppressive properties. However, RPE cells are also known as immunogenic cells, and they have major histocompatibility complex expression and produce inflammatory proteins, and thus experience immune rejection after transplantation. In this study, to confirm the immunological properties of IPS-RPE cells, we examined whether human RPE cells derived from iPS cells could suppress or stimulate inflammatory T cells from uveitis patients via costimulatory signals. We established T cells from patients with active uveitis as target cells and used iPS-RPE cells as effector cells. As a result, cultured iPS-RPE cells inhibited cell proliferation and the production of IFN-γ by activated uveitis CD4+ T cells, especially Th1-type T cells. In contrast, iPS-RPE cells stimulated T cells of uveitis patients. The iPS-RPE cells constitutively expressed B7-H1/CD274 and B7-DC/CD273, and suppressed the activation of T cells via the PD-1 receptor. iPS-RPE expressed these negative costimulatory molecules, especially when RPE cells were pretreated with recombinant IFN-γ. In addition, iPS-RPE cells also expressed B7-H3/CD276 costimulatory molecules and activated uveitis T cells through the B7-H3-TLT-2 receptor. Thus, cultured iPS-derived retinal cells can suppress or activate inflammatory T cells in vitro through costimulatory interactions.
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Rajendran Nair, Deepthi S., Danhong Zhu, Ruchi Sharma, Juan Carlos Martinez Camarillo, Kapil Bharti, David R. Hinton, Mark S. Humayun, and Biju B. Thomas. "Long-Term Transplant Effects of iPSC-RPE Monolayer in Immunodeficient RCS Rats." Cells 10, no. 11 (October 29, 2021): 2951. http://dx.doi.org/10.3390/cells10112951.
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Retinal pigment epithelium (RPE) replacement therapy is evolving as a feasible approach to treat age-related macular degeneration (AMD). In many preclinical studies, RPE cells are transplanted as a cell suspension into immunosuppressed animal eyes and transplant effects have been monitored only short-term. We investigated the long-term effects of human Induced pluripotent stem-cell-derived RPE (iPSC-RPE) transplants in an immunodeficient Royal College of Surgeons (RCS) rat model, in which RPE dysfunction led to photoreceptor degeneration. iPSC-RPE cultured as a polarized monolayer on a nanoengineered ultrathin parylene C scaffold was transplanted into the subretinal space of 28-day-old immunodeficient RCS rat pups and evaluated after 1, 4, and 11 months. Assessment at early time points showed good iPSC-RPE survival. The transplants remained as a monolayer, expressed RPE-specific markers, performed phagocytic function, and contributed to vision preservation. At 11-months post-implantation, RPE survival was observed in only 50% of the eyes that were concomitant with vision preservation. Loss of RPE monolayer characteristics at the 11-month time point was associated with peri-membrane fibrosis, immune reaction through the activation of macrophages (CD 68 expression), and the transition of cell fate (expression of mesenchymal markers). The overall study outcome supports the therapeutic potential of RPE grafts despite the loss of some transplant benefits during long-term observations.
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Niu, Yali, Yixuan Xi, Yutong Jing, Ziyi Zhou, Xiaojia Sun, Guoheng Zhang, Tianhao Yuan, Tianfang Chang, and Guorui Dou. "Endothelial Notch Signaling Regulates the Function of the Retinal Pigment Epithelial Barrier via EC Angiocrine Signaling." Antioxidants 12, no. 11 (November 7, 2023): 1979. http://dx.doi.org/10.3390/antiox12111979.
Full textAbstract:
The outer blood–retina barrier (oBRB), comprises tightly connected retinal pigment epithelium (RPE) cells, Bruch’s membrane, and choroid blood vessels, and is essential for retinal health and normal visual function. Disruption of the RPE barrier and its dysfunction can lead to retinal disorders such as age-related macular degeneration (AMD). In the present study, we investigated the essential role of choroid endothelial cells (ECs) in the RPE barrier formation process and its dysfunction. We discovered that ECs promoted RPE barrier formation through angiocrine signaling. Through blocking or activating endothelial Notch signaling and conducting experiments in vitro and in vivo, we confirmed that endothelial Notch signaling regulated the expression of heparin-binding epidermal growth factor (HBEGF) and consequently impacted the expression and activity of matrix metalloproteinases (MMP)-9 in RPE cells. This modulation influenced the RPE extracellular matrix deposition, tight junctions and RPE barrier function. In in vivo experiments, the intravitreal administration of recombinant HBEGF (r-HBEGF) alleviated the RPE barrier disruption induced by subretinal injection (SI) or laser treatment and also rescued RPE barrier disruption in endothelial Notch-deficient mice. Our results showed that the endothelial Notch signaling drove HBEGF expression through angiocrine signaling and effectively improved RPE barrier function by regulating the MMP-9 expression in RPE cells. It suggests that the modulation of Notch signaling in the choroidal endothelium may offer a novel therapeutic strategy for retinal degenerative diseases.
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Guidetti, Laura, Antonio Sgadari, Cosme F. Buzzachera, Marianna Broccatelli, Alan C. Utter, Fredric L. Goss, and Carlo Baldari. "Validation of the OMNI-Cycle Scale of Perceived Exertion in the Elderly." Journal of Aging and Physical Activity 19, no. 3 (July 2011): 214–24. http://dx.doi.org/10.1123/japa.19.3.214.
Full textAbstract:
This study examined the concurrent and construct validity of the OMNI-Cycle Rating of Perceived Exertion (RPE) Scale, using elderly men and women. Seventy-six participants performed a load-incremented cycle-ergometer exercise test. Concurrent validity was determined by correlating OMNI-RPE responses with oxygen uptake, relative peak oxygen uptake, pulmonary ventilation, heart rate, respiratory rate, and respiratory-exchange ratio during a load-incremented cycle-ergometer protocol. Construct validity was established by correlating RPE derived from the OMNI-Cycle Scale with RPE from the Borg (6–20) Scale. Multilevel, mixed linear-regression models indicated that OMNI-RPE distributed as a significant (p< .05) positive linear function (r= .81–.92) for all physiological measures. OMNI-RPE was positively (p< .01) and linearly related to Borg-RPE in elderly men (r= .97) and women (r= .96). This study demonstrates both concurrent and construct validity of the OMNI-Cycle RPE Scale. These findings support the use of this scaling metric with elderly men and women to estimate RPE during cycle-ergometer exercise.
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Du, Jianhai, Aya Yanagida, Kaitlen Knight, Abbi L. Engel, Anh Huan Vo, Connor Jankowski, Martin Sadilek, et al. "Reductive carboxylation is a major metabolic pathway in the retinal pigment epithelium." Proceedings of the National Academy of Sciences 113, no. 51 (December 1, 2016): 14710–15. http://dx.doi.org/10.1073/pnas.1604572113.
Full textAbstract:
The retinal pigment epithelium (RPE) is a monolayer of pigmented cells that requires an active metabolism to maintain outer retinal homeostasis and compensate for oxidative stress. Using13C metabolic flux analysis in human RPE cells, we found that RPE has an exceptionally high capacity for reductive carboxylation, a metabolic pathway that has recently garnered significant interest because of its role in cancer cell survival. The capacity for reductive carboxylation in RPE exceeds that of all other cells tested, including retina, neural tissue, glial cells, and a cancer cell line. Loss of reductive carboxylation disrupts redox balance and increases RPE sensitivity to oxidative damage, suggesting that deficiencies of reductive carboxylation may contribute to RPE cell death. Supporting reductive carboxylation by supplementation with an NAD+precursor or its substrate α-ketoglutarate or treatment with a poly(ADP ribose) polymerase inhibitor protects reductive carboxylation and RPE viability from excessive oxidative stress. The ability of these treatments to rescue RPE could be the basis for an effective strategy to treat blinding diseases caused by RPE dysfunction.
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Clemens, Christoph R., and Nicole Eter. "Retinal Pigment Epithelium Tears: Risk Factors, Mechanism and Therapeutic Monitoring." Ophthalmologica 235, no. 1 (October 22, 2015): 1–9. http://dx.doi.org/10.1159/000439445.
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Tears of the retinal pigment epithelium (RPE) are most commonly associated with vascularised RPE detachment due to age-related macular degeneration (AMD), and they usually involve a deleterious loss in visual acuity. Recent studies suggest an increase in RPE tear incidences since the introduction of anti-vascular endothelial growth factor (anti-VEGF) therapies as well as a temporal association between the tear event and the intravitreal injection. As the number of AMD patients and the number of administered anti-VEGF injections increase, both the challenge of RPE tear prevention and the treatment after RPE tear formation have become more important. At the same time, the evolution of retinal imaging has significantly contributed to a better understanding of RPE tear development in recent years. This review summarises the current knowledge on RPE tear development, predictive factors, and treatment strategies before and after RPE tear formation.