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1
Terao, Ryo, and Hiroki Kaneko. "Lipid Signaling in Ocular Neovascularization." International Journal of Molecular Sciences 21, no. 13 (July 4, 2020): 4758. http://dx.doi.org/10.3390/ijms21134758.
Повний текст джерелаАнотація:
Vasculogenesis and angiogenesis play a crucial role in embryonic development. Pathological neovascularization in ocular tissues can lead to vision-threatening vascular diseases, including proliferative diabetic retinopathy, retinal vein occlusion, retinopathy of prematurity, choroidal neovascularization, and corneal neovascularization. Neovascularization involves various cellular processes and signaling pathways and is regulated by angiogenic factors such as vascular endothelial growth factor (VEGF) and hypoxia-inducible factor (HIF). Modulating these circuits may represent a promising strategy to treat ocular neovascular diseases. Lipid mediators derived from membrane lipids are abundantly present in most tissues and exert a wide range of biological functions by regulating various signaling pathways. In particular, glycerophospholipids, sphingolipids, and polyunsaturated fatty acids exert potent pro-angiogenic or anti-angiogenic effects, according to the findings of numerous preclinical and clinical studies. In this review, we summarize the current knowledge regarding the regulation of ocular neovascularization by lipid mediators and their metabolites. A better understanding of the effects of lipid signaling in neovascularization may provide novel therapeutic strategies to treat ocular neovascular diseases and other human disorders.
2
L., J. F. "VASCULAR ENDOTHELIAL GROWTH FACTOR IN OCULAR FLUID OF PATIENTS WITH DIABETIC RETINOPATHY AND OTHER RETINAL DISORDERS." Pediatrics 95, no. 3 (March 1, 1995): A44. http://dx.doi.org/10.1542/peds.95.3.a44.
Повний текст джерелаАнотація:
Background. Retinal ischemia induces intraocular neovascularization, which often leads to glaucoma, vitreous hemorrhage, and retinal detachment, presumably by stimulating the release of angiogenic molecules. Vascular endothelial growth factor (VEGF) is an endothelial-cell-specific angiogenic factor whose production is increased by hypoxia. Conclusions. Our data suggest that VEGF plays a major part in mediating active intraocular neovascularization in patients with ischemic retinal diseases, such as diabetic retinopathy and retinal-vein occlusion.
3
Bainbridge, James W., Vanya Loroch, Eric Viaud, and Claus Cursiefen. "Beyond Anti-VEGFs – Anti-Insulin Receptor Substrate-1 Oligonucleotides as a Novel Approach to Ocular Neovascular Disorders." European Ophthalmic Review 06, no. 03 (2012): 190. http://dx.doi.org/10.17925/eor.2012.06.03.190.
Повний текст джерелаАнотація:
Angiogenesis is a complex process that is vital to health but is also a driving factor behind a broad range of malignant, ischaemic, inflammatory, infectious and immune disorders. For optimal efficacy and safety, therapies aimed at preventing angiogenic-mediated disorders must differentiate between healthy and pathological angiogenesis or neovascularisation. Aganirsen is an antisense oligonucleotide that inhibits the insulin receptor substrate (IRS)-1 angiogenic pathway by targeting the IRS-1 messenger RNA. To date, studies of aganirsen have focused mainly on ocular disorders because of the ability to assess non-invasively the effect of the drug on neovascularisation and to address the unmet need for effective therapies in these blinding disorders. Aganirsen (GS-101) eye drops inhibit progressive corneal neovascularisation and appear to be well tolerated. The drug may offer an alternative and/or adjunct to intraocular anti-vascular endothelial cell growth factor (VEGF) agents, which are the current reference standards to prevent neovascularisation in retinal diseases. This is because it has a different and potentially complementary mechanism of action and can be administered topically. Antisense oligonucleotides targeting IRS-1 may present a valuable new approach to control pathological angiogenesis in the eye and elsewhere.
4
Gadzhieva, Banovsha K. "Ocular neovascular-related diseases: immunological mechanisms of development and the potential of anti-angiogenic therapy." Ophthalmology journal 9, no. 4 (December 15, 2016): 58–67. http://dx.doi.org/10.17816/ov9458-67.
Повний текст джерелаАнотація:
The paper adresses three ocular diseases - “wet” type of age-related macular degeneration, diabetic macular edema and neovascular glaucoma, which have similar neovascular changes and immunological disorders. The key moment of neovascularization development is an imbalance between pro- and anti-angiogenic factors. Particular attention is paid to vascular endothelial growth factor (VEGF-A), pigment epithelial derived factor (PEDF), transforming growth factor-beta (ТGF-β). The paper discusses the “immune privilege” of the eye, ACAID phenomenon, aspects of choroidal neovascularization pathogenesis, inflammation as an important part of neovascularization and the protective response to endogenous and exogenous damage, as well as complement system’s disorders, cytokine status impairment and autoimmune mechanisms. Laser treatment is widely used for treatment of neovascular diseases, but pharmacotherapy is very important too. Anti-angiogenic therapy is extremely promising and is held to provide regression of the newly-formed vasculature and/or normalization of newly formed blood vessels structure and suppress the functional activity of a key proangiogenic factor VEGF-A. Pegaptanib, ranibizumab and bevacizumab are discussed, and results of international clinical trials MARINA, ANCHOR, FOCUS, PrONTO, IVAN, CATT, RESTORE are provided.
5
Ewa Choy, Yee Wa, Ker Woon Choy, Kai Siong Woon, Muhammad Aidil Wafi, Kong Yong Then, and Khong Lek Then. "Genetically Engineered Mesenchymal Stem Cells Using Viral Vectors: A New Frontier in Anti-Angiogenic Therapy." Sains Malaysiana 53, no. 1 (January 31, 2024): 63–86. http://dx.doi.org/10.17576/jsm-2024-5301-06.
Повний текст джерелаАнотація:
Mesenchymal stem cells (MSCs) are adult stem cells that possess the remarkable ability to self-renew and differentiate into various cell lineages. Due to their regenerative potential, MSCs have emerged as the most commonly used stem cell type in clinical applications. Angiogenesis, the formation of new blood vessels, plays a critical role in several pathological conditions, including ocular neovascular diseases, cancer, and inflammatory disorders. Conventional anti-angiogenic therapies face limitations such as frequent visits for repeated doses, off-target effects and resistance development. Recent advances in genetic engineering techniques have opened up novel avenues in regenerative medicine. Genetically engineering MSCs using viral vectors presents a promising strategy to specifically target angiogenesis and enhance anti-angiogenic therapies' efficacy. Viral vectors, including lentiviruses, adeno-associated viruses and adenoviruses, provide an effective means of delivering therapeutic genes into MSCs, allowing the expression of a wide range of therapeutic agents, including anti-angiogenic proteins. This review explores the frontier of using genetically engineered MSCs delivered through viral vectors as a potent anti-angiogenic therapeutic approach. By leveraging the unique properties of MSCs and the targeted delivery capabilities of viral vectors, this approach initiates the potential to revolutionize anti-angiogenic therapy, offering new possibilities for the treatment of angiogenesis-related diseases.
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Anitua, Eduardo, Francisco Muruzabal, Ander Pino, Roberto Prado, Mikel Azkargorta, Felix Elortza, and Jesús Merayo-Lloves. "Proteomic Characterization of Plasma Rich in Growth Factors and Undiluted Autologous Serum." International Journal of Molecular Sciences 22, no. 22 (November 10, 2021): 12176. http://dx.doi.org/10.3390/ijms222212176.
Повний текст джерелаАнотація:
Over the last three decades, there has been special interest in developing drugs that mimic the characteristics of natural tears for use it in the treatment of several ocular surface disorders. Interestingly, the composition of blood plasma is very similar to tears. Therefore, different blood-derived products like autologous serum (AS) and plasma rich in growth factors (PRGF) have been developed for the treatment of diverse ocular pathologies. However, scarce studies have been carried out to analyze the differences between both types of blood-derived products. In the present study, blood from three healthy donors was drawn and processed to obtain AS and PRGF eye drops. Then, human corneal stromal keratocytes (HK) were treated with PRGF or undiluted AS. Proteomic analysis was carried out to analyze and characterize the differential protein profiles between PRGF and AS, and the differentially expressed proteins in HK cells after PRGF and AS treatment. The results obtained in the present study show that undiluted AS induces the activation of different pathways related to an inflammatory, angiogenic, oxidative stress and scarring response in HK cells regarding PRGF. These results suggest that PRGF could be a better alternative than AS for the treatment of ocular surface disorders.
7
du Toit, Lisa Claire, Yahya Essop Choonara, and Viness Pillay. "An Injectable Nano-Enabled Thermogel to Attain Controlled Delivery of p11 Peptide for the Potential Treatment of Ocular Angiogenic Disorders of the Posterior Segment." Pharmaceutics 13, no. 2 (January 28, 2021): 176. http://dx.doi.org/10.3390/pharmaceutics13020176.
Повний текст джерелаАнотація:
This investigation focused on the design of an injectable nano-enabled thermogel (nano-thermogel) system to attain controlled delivery of p11 anti-angiogenic peptide for proposed effective prevention of neovascularisation and to overcome the drawbacks of the existing treatment approaches for ocular disorders characterised by angiogenesis, which employ multiple intravitreal injections of anti-vascular endothelial growth factor (anti-VEGF) antibodies. Synthesis of a polyethylene glycol-polycaprolactone-polyethylene glycol (PEG-PCL-PEG) triblock co-polymer was undertaken, followed by characterisation employing Fourier-transform infrared (FTIR) spectroscopy, nuclear magnetic resonance (NMR) spectroscopy and differential scanning calorimetry (DSC) to ascertain the chemical stability and integrity of the co-polymer instituted for nano-thermogel formulation. The p11 anti-angiogenic peptide underwent encapsulation within poly(lactic-co-glycolic acid) (PLGA) nanoparticles via a double emulsion solvent evaporation method and was incorporated into the thermogel following characterisation by scanning electron microscopy (SEM), zeta size and zeta-potential analysis. The tube inversion approach and rheological analysis were employed to ascertain the thermo-sensitive sol-gel conversion of the nano-thermogel system. Chromatographic assessment of the in vitro release of the peptide was performed, with stability confirmation via Tris-Tricine PAGE (Polyacrylamide Gel Electrophoresis). In vitro biocompatibility of the nano-thermogel system was investigated employing a retinal cell line (ARP-19). A nanoparticle size range of 100–200 nm and peptide loading efficiency of 67% was achieved. Sol-gel conversion of the nano-thermogel was observed between 32–45 °C. Release of the peptide in vitro was sustained, with maintenance of stability, for 60 days. Biocompatibility assessment highlighted 97–99% cell viability with non-haemolytic ability, which supports the potential applicability of the nano-thermogel system for extended delivery of peptide for ocular disorder treatment.
8
Hong, Yiwen, and Yan Luo. "Zebrafish Model in Ophthalmology to Study Disease Mechanism and Drug Discovery." Pharmaceuticals 14, no. 8 (July 25, 2021): 716. http://dx.doi.org/10.3390/ph14080716.
Повний текст джерелаАнотація:
Visual impairment and blindness are common and seriously affect people’s work and quality of life in the world. Therefore, the effective therapies for eye diseases are of high priority. Zebrafish (Danio rerio) is an alternative vertebrate model as a useful tool for the mechanism elucidation and drug discovery of various eye disorders, such as cataracts, glaucoma, diabetic retinopathy, age-related macular degeneration, photoreceptor degeneration, etc. The genetic and embryonic accessibility of zebrafish in combination with a behavioral assessment of visual function has made it a very popular model in ophthalmology. Zebrafish has also been widely used in ocular drug discovery, such as the screening of new anti-angiogenic compounds or neuroprotective drugs, and the oculotoxicity test. In this review, we summarized the applications of zebrafish as the models of eye disorders to study disease mechanism and investigate novel drug treatments.
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Caban, Miłosz, and Urszula Lewandowska. "Vitamin D, the Vitamin D Receptor, Calcitriol Analogues and Their Link with Ocular Diseases." Nutrients 14, no. 11 (June 5, 2022): 2353. http://dx.doi.org/10.3390/nu14112353.
Повний текст джерелаАнотація:
The global prevalence of eye diseases continues to grow, bringing with it a reduction in the activity levels and quality of life of patients, and partial or complete blindness if left untreated. As such, there is considerable interest in identifying more effective therapeutic options and preventive agents. One such agent is vitamin D, known to have a range of anti-cancer, anti-angiogenic, anti-inflammatory and anti-oxidative properties, and whose deficiency is linked to the pathogenesis of a range of cardiovascular, cancer, and inflammatory diseases. This review presents the current stage of knowledge concerning the link between vitamin D and its receptor and the occurrence of eye disease, as well as the influence of analogues of calcitriol, an active metabolite of vitamin D. Generally, patients affected by various ocular disorders have vitamin D deficiency. In addition, previous findings suggest that vitamin D modulates the course of eye diseases and may serve as a marker, and that its supplementation could mitigate some disorders. However, as these studies have some limitations, we recommend further randomized trials to clarify the link between vitamin D and its activity with eye disease.
10
Aghazadeh, Sara, Qiuyue Peng, Fereshteh Dardmeh, Jesper Østergaard Hjortdal, Vladimir Zachar, and Hiva Alipour. "Immunophenotypical Characterization of Limbal Mesenchymal Stromal Cell Subsets during In Vitro Expansion." International Journal of Molecular Sciences 25, no. 16 (August 9, 2024): 8684. http://dx.doi.org/10.3390/ijms25168684.
Повний текст джерелаАнотація:
Limbal mesenchymal stromal cells (LMSCs) reside in the limbal niche, supporting corneal integrity and facilitating regeneration. While mesenchymal stem/stromal cells (MSCs) are used in regenerative therapies, there is limited knowledge about LMSC subpopulations and their characteristics. This study characterized human LMSC subpopulations through the flow cytometric assessment of fifteen cell surface markers, including MSC, wound healing, immune regulation, ASC, endothelial, and differentiation markers. Primary LMSCs were established from remnant human corneal transplant specimens and passaged eight times to observe changes during subculture. The results showed the consistent expression of typical MSC markers and distinct subpopulations with the passage-dependent expression of wound healing, immune regulation, and differentiation markers. High CD166 and CD248 expressions indicated a crucial role in ocular surface repair. CD29 expression suggested an immunoregulatory role. Comparable pigment-epithelial-derived factor (PEDF) expression supported anti-inflammatory and anti-angiogenic roles. Sustained CD201 expression indicated maintained differentiation capability, while VEGFR2 expression suggested potential endothelial differentiation. LMSCs showed higher VEGF expression than fibroblasts and endothelial cells, suggesting a potential contribution to ocular surface regeneration through the modulation of angiogenesis and inflammation. These findings highlight the heterogeneity and multipotent potential of LMSC subpopulations during in vitro expansion, informing the development of standardized protocols for regenerative therapies and improving treatments for ocular surface disorders.
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Balzamino, Bijorn Omar, Andrea Cacciamani, Lucia Dinice, Michela Cecere, Francesca Romana Pesci, Guido Ripandelli, and Alessandra Micera. "Retinal Inflammation and Reactive Müller Cells: Neurotrophins’ Release and Neuroprotective Strategies." Biology 13, no. 12 (December 9, 2024): 1030. https://doi.org/10.3390/biology13121030.
Повний текст джерелаАнотація:
Millions of people worldwide suffer from retinal disorders. Retinal diseases require prompt attention to restore function or reduce progressive impairments. Genetics, epigenetics, life-styling/quality and external environmental factors may contribute to developing retinal diseases. In the physiological retina, some glial cell types sustain neuron activities by guaranteeing ion homeostasis and allowing effective interaction in synaptic transmission. Upon insults, glial cells interact with neuronal and the other non-neuronal retinal cells, at least in part counteracting the biomolecular changes that may trigger retinal complications and vision loss. Several epigenetic and oxidative stress mechanisms are quickly activated to release factors that in concert with growth, fibrogenic and angiogenic factors can influence the overall microenvironment and cell-to-cell response. Reactive Müller cells participate by secreting neurotrophic/growth/angiogenic factors, cytokines/chemokines, cytotoxic/stress molecules and neurogenic inflammation peptides. Any attempt to maintain/restore the physiological condition can be interrupted by perpetuating insults, vascular dysfunction and neurodegeneration. Herein, we critically revise the current knowledge on the cell-to-cell and cell-to-mediator interplay between Müller cells, astrocytes and microglia, with respect to pro-con modulators and neuroprotective/detrimental activities, as observed by using experimental models or analyzing ocular fluids, altogether contributing a new point of view to the field of research on precision medicine.
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Choubey, Mayank, Munichandra B. Tirumalasetty, Nalini S. Bora, and Puran S. Bora. "Linking Adiponectin and Its Receptors to Age-Related Macular Degeneration (AMD)." Biomedicines 11, no. 11 (November 14, 2023): 3044. http://dx.doi.org/10.3390/biomedicines11113044.
Повний текст джерелаАнотація:
In recent years, there has been a captivating focus of interest in elucidating the intricate crosstalk between adiponectin (APN), a versatile fat-associated adipokine and ocular pathologies. Unveiling the intricate relationship between adipocytokine APN and its receptors (AdipoRs) with aging eye disorders has emerged as a fascinating frontier in medical research. This review article delves into this connection, illuminating the hidden influence of APN on retinal health. This comprehensive review critically examines the latest findings and breakthroughs that underscore the pivotal roles of APN/AdipoRs signaling in maintaining ocular homeostasis and protecting against eye ailments. Here, we meticulously explore the intriguing mechanisms by which APN protein influences retinal function and overall visual acuity. Drawing from an extensive array of cutting-edge studies, the article highlights APN’s multifaceted functions, ranging from anti-inflammatory properties and oxidative stress reduction to angiogenic regulation within retinal and macula tissues. The involvement of APN/AdipoRs in mediating these effects opens up novel avenues for potential therapeutic interventions targeting prevalent aging eye conditions. Moreover, this review unravels the interplay between APN signaling pathways and age-related macular degeneration (AMD). The single-cell RNA-seq results validate the expression of both the receptor isoforms (AdipoR1/R2) in retinal cells. The transcriptomic analysis showed lower expression of AdipoR1/2 in dry AMD pathogenesis compared to healthy subjects. The inhibitory adiponectin peptide (APN1) demonstrated over 75% suppression of CNV, whereas the control peptide did not exert any inhibitory effect on choroidal neovascularization (CNV). The elucidation of these relationships fosters a deeper understanding of adipose tissue’s profound influence on ocular health, presenting new prospects for personalized treatments and preventative measures. Because APN1 inhibits CNV and leakage, it can be used to treat human AMD, although the possibility to treat human AMD is in the early stage and more clinical research is needed. In conclusion, this review provides a captivating journey into the enthralling world of APN, intertwining the realms of adipose biology and ophthalmology in aging.
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Parmar, Tanu, Joseph T. Ortega, and Beata Jastrzebska. "Retinoid analogs and polyphenols as potential therapeutics for age-related macular degeneration." Experimental Biology and Medicine 245, no. 17 (May 21, 2020): 1615–25. http://dx.doi.org/10.1177/1535370220926938.
Повний текст джерелаАнотація:
Progressive retinal degeneration manifesting as age-related macular degeneration (AMD) in the elderly affects millions of individuals worldwide. Among various blinding diseases, AMD is the leading cause of central vision impairment in developed countries. Poor understanding of AMD etiology hampers the development of therapeutics against this devastating ocular disease. Currently, daily intravitreal injections of anti-angiogenic drugs, preventing abnormal vessel growth are the only treatment option for wet AMD. However, for dry AMD associated with retinal atrophy, at present there is no cure available. Recent clinical research has demonstrated beneficial effects of plant-derived compounds for various eye disorders. Thus, the ongoing efforts toward discovering efficient treatments preventing or delaying AMD progression focus on implementing a healthy diet rich in vitamins, including vitamin A, E, and C, minerals and carotenoids, in particular lutein and zeaxanthin, to reduce the disease burden. In addition, studies in cell culture and animal models indicated therapeutic potential of dietary polyphenolic compounds present in fruits and vegetables. These natural compounds protect visual function and retinal morphology likely due to their anti-oxidant and anti-inflammatory properties. Although understanding of the exact mechanism of these compounds’ positive effects requires further investigation, they provide non-invasive alternative to battle AMD-like condition. Additionally, studies carried in animal models mimicking AMD-like pathology, examining the pharmacological potential of particular retinoid analogs, demonstrated promising results for their use, and thus they should be considered as an option in developing therapies for AMD. In here, we summarize the most current knowledge regarding developments of therapeutic options to maintain ocular health and prevent vision loss associated with aging. Impact statement Age-related macular degeneration (AMD) is a devastating retinal degenerative disease. Epidemiological reports showed an expected increasing prevalence of AMD in the near future. The only one existing FDA-approved pharmacological treatment involves an anti-vascular endothelial growth factor (VEGF) therapy with serious disadvantages. This limitation emphasizes an alarming need to develop new therapeutic approaches to prevent and treat AMD. In this review, we summarize scientific data unraveling the therapeutic potential of the specific retinoid and natural compounds. The experimental results reported by us and other research groups demonstrated that retinoid analogs and compounds with natural product scaffolds could serve as lead compounds for the development of new therapeutic agents with potential to prevent or slow down the pathogenesis of AMD.
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Mallone, Fabiana, Roberta Costi, Marco Marenco, Rocco Plateroti, Antonio Minni, Giuseppe Attanasio, Marco Artico, and Alessandro Lambiase. "Understanding Drivers of Ocular Fibrosis: Current and Future Therapeutic Perspectives." International Journal of Molecular Sciences 22, no. 21 (October 29, 2021): 11748. http://dx.doi.org/10.3390/ijms222111748.
Повний текст джерелаАнотація:
Ocular fibrosis leads to severe visual impairment and blindness worldwide, being a major area of unmet need in ophthalmology and medicine. To date, the only available treatments are antimetabolite drugs that have significant potentially blinding side effects, such as tissue damage and infection. There is thus an urgent need to identify novel targets to prevent/treat scarring and postsurgical fibrosis in the eye. In this review, the latest progress in biological mechanisms underlying ocular fibrosis are discussed. We also summarize the current knowledge on preclinical studies based on viral and non-viral gene therapy, as well as chemical inhibitors, for targeting TGFβ or downstream effectors in fibrotic disorders of the eye. Moreover, the role of angiogenetic and biomechanical factors in ocular fibrosis is discussed, focusing on related preclinical treatment approaches. Moreover, we describe available evidence on clinical studies investigating the use of therapies targeting TGFβ-dependent pathways, angiogenetic factors, and biomechanical factors, alone or in combination with other strategies, in ocular tissue fibrosis. Finally, the recent progress in cell-based therapies for treating fibrotic eye disorders is discussed. The increasing knowledge of these disorders in the eye and the promising results from testing of novel targeted therapies could offer viable perspectives for translation into clinical use.
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Oladnabi, Morteza, Mohammad Amir Mishan, Mozhgan Rezaeikanavi, Mehryar Zargari, Rouhallah Najjar Sadeghi, and Abouzar Bagheri. "Correlation between ELF–PEMF exposure and Human RPE Cell Proliferation, Apoptosis and Gene Expression." Journal of Ophthalmic and Vision Research, April 29, 2021. http://dx.doi.org/10.18502/jovr.v16i2.9084.
Повний текст джерелаАнотація:
Purpose: Emerging evidence implies that electromagnetic fields (EMFs) can negatively affect angiogenesis. In this regard, the effects of extremely low frequency pulsed electromagnetic field (ELF–PEMF) exposure on the relative expression level of angiogenic factors involved in the pathogenesis of ocular disorders were evaluated in human retinal pigment epithelial (hRPE) cells in order to investigate a noninvasive therapeutic method for patients with several ocular diseases associated with neovascularization.
Methods: After separating hRPE cells from globes, hRPE cells were exposed to 15 mT of ELF–PEMF (120 Hz) at 5, 10, and 15 min for seven days. Cell proliferation and apoptosis of treated cells were evaluated via ELISA assay. Moreover, relative expression changes of HIF-1α, CTGF, VEGFA, MMP-2, cathepsin D, and E2F3 were performed using real-time RT-PCR.
Results: ELF–PEMF exposure had no significant effects on the apoptosis and proliferation rate of hRPE cells. Expression level of HIF-1α, CTGF, VEGFA, MMP- 2, cathepsin D, and E2F3 was downregulated following 5 min of ELF–PEMF exposure.
Conclusion: As ELF–PEMF showed inhibitory effects on the expression of angiogenic genes in hRPE cells with no cytotoxic or proliferative side effects, it can be introduced as a useful procedure for managing angiogenesis induced by retinal pathogenesis, although more studies with adequate follow-up in animal models are needed.
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Chung, Sook Hyun, Tzu-Ni Sin, Taylor Ngo, and Glenn Yiu. "CRISPR Technology for Ocular Angiogenesis." Frontiers in Genome Editing 2 (December 22, 2020). http://dx.doi.org/10.3389/fgeed.2020.594984.
Повний текст джерелаАнотація:
Among genome engineering tools, Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-based approaches have been widely adopted for translational studies due to their robustness, precision, and ease of use. When delivered to diseased tissues with a viral vector such as adeno-associated virus, direct genome editing can be efficiently achieved in vivo to treat different ophthalmic conditions. While CRISPR has been actively explored as a strategy for treating inherited retinal diseases, with the first human trial recently initiated, its applications for complex, multifactorial conditions such as ocular angiogenesis has been relatively limited. Currently, neovascular retinal diseases such as retinopathy of prematurity, proliferative diabetic retinopathy, and neovascular age-related macular degeneration, which together constitute the majority of blindness in developed countries, are managed with frequent and costly injections of anti-vascular endothelial growth factor (anti-VEGF) agents that are short-lived and burdensome for patients. By contrast, CRISPR technology has the potential to suppress angiogenesis permanently, with the added benefit of targeting intracellular signals or regulatory elements, cell-specific delivery, and multiplexing to disrupt different pro-angiogenic factors simultaneously. However, the prospect of permanently suppressing physiologic pathways, the unpredictability of gene editing efficacy, and concerns for off-target effects have limited enthusiasm for these approaches. Here, we review the evolution of gene therapy and advances in adapting CRISPR platforms to suppress retinal angiogenesis. We discuss different Cas9 orthologs, delivery strategies, and different genomic targets including VEGF, VEGF receptor, and HIF-1α, as well as the advantages and disadvantages of genome editing vs. conventional gene therapies for multifactorial disease processes as compared to inherited monogenic retinal disorders. Lastly, we describe barriers that must be overcome to enable effective adoption of CRISPR-based strategies for the management of ocular angiogenesis.
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Hopkinson, Andrew, Maria Notara, Claus Cursiefen, and Laura E. Sidney. "Increased Anti-Inflammatory Therapeutic Potential and Progenitor Marker Expression of Corneal Mesenchymal Stem Cells Cultured in an Optimized Propagation Medium." Cell Transplantation 33 (January 2024). http://dx.doi.org/10.1177/09636897241241992.
Повний текст джерелаАнотація:
There is a huge unmet need for new treatment modalities for ocular surface inflammatory disorders (OSIDs) such as dry eye disease and meibomian gland dysfunction. Mesenchymal stem cell therapies may hold the answer due to their potent immunomodulatory properties, low immunogenicity, and ability to modulate both the innate and adaptive immune response. MSC-like cells that can be isolated from the corneal stroma (C-MSCs) offer a potential new treatment strategy; however, an optimized culture medium needs to be developed to produce the ideal phenotype for use in a cell therapy to treat OSIDs. The effects of in vitro expansion of human C-MSC in a medium of M199 containing fetal bovine serum (FBS) was compared to a stem cell medium (SCM) containing knockout serum replacement (KSR) with basic fibroblast growth factor (bFGF) and human leukemia inhibitory factor (LIF), investigating viability, protein, and gene expression. Isolating populations expressing CD34 or using siRNA knockdown of CD34 were investigated. Finally, the potential of C-MSC as a cell therapy was assessed using co-culture with an in vitro corneal epithelial cell injury model and the angiogenic effects of C-MSC conditioned medium were evaluated with blood and lymph endothelial cells. Both media supported proliferation of C-MSC, with SCM increasing expression of CD34, ABCG2, PAX6, NANOG, REX1, SOX2, and THY1, supported by increased associated protein expression. Isolating cell populations expressing CD34 protein made little difference to gene expression, however, knockdown of the CD34 gene led to decreased expression of progenitor genes. C-MSC increased viability of injured corneal epithelial cells whilst decreasing levels of cytotoxicity and interleukins-6 and -8. No pro-angiogenic effect of C-MSC was seen. Culture medium can significantly influence C-MSC phenotype and culture in SCM produced a cell phenotype more suitable for further consideration as an anti-inflammatory cell therapy. C-MSC show considerable potential for development as therapies for OSIDs, acting through anti-inflammatory action.
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Zhang, Yichi, Xiaojing Zhao, Yang Liu, and Xiuxia Yang. "Sulforaphane and ophthalmic diseases." Food Science & Nutrition, May 22, 2024. http://dx.doi.org/10.1002/fsn3.4230.
Повний текст джерелаАнотація:
AbstractSulforaphane (SFN) is an organosulfur compound categorized as an isothiocyanate (ITC), primarily extracted from cruciferous vegetables like broccoli and cabbage. The molecular formula of sulforaphane (SFN) is C6H11NOS2. SFN is generated by the hydrolysis of glucoraphanin (GRP) through the enzyme myrosinase, showing notable properties including anti‐diabetic, anti‐inflammatory, antimicrobial, anti‐angiogenic, and anticancer attributes. Ongoing clinical trials are investigating its potential in diseases such as cancer, neurodegenerative diseases, diabetes‐related complications, chronic kidney disease, cardiovascular disease, and liver diseases. Several animal carcinogenesis models and cell culture models have shown it to be a very effective chemopreventive agent, and the protective effects of SFN in ophthalmic diseases have been linked to multiple mechanisms. In murine models of diabetic retinopathy and age‐related macular degeneration, SFN delays retinal photoreceptor cell degeneration through the Nrf2 antioxidative pathway, NF‐κB pathway, AMPK pathway, and Txnip/mTOR pathway. In rabbit models of keratoconus and cataract, SFN has been shown to protect corneal and lens epithelial cells from oxidative stress injury by activating the Keap1‐Nrf2‐ARE pathway and the Nrf‐2/HO‐1 antioxidant pathway. Oral delivery or intraperitoneal injection at varying concentrations are the primary strategies for SFN intake in current preclinical studies. Challenges remain in the application of SFN in eye disorders due to its weak solubility in water and limited bioavailability because of the presence of blood–ocular barrier systems. This review comprehensively outlines recent research on SFN, elucidates its mechanisms of action, and discusses potential therapeutic benefits for eye disorders such as age‐related macular degeneration (AMD), diabetic retinopathy (DR), cataracts, and other ophthalmic diseases, while also indicating directions for future clinical research to achieve efficient SFN treatment for ophthalmic diseases.
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Rad, Lina Moallemi, Alexey V. Yumashev, Bashdar Mahmud Hussen, Hazha Hadayat Jamad, Soudeh Ghafouri-Fard, Mohammad Taheri, Samaneh Rostami, Vahid Niazi, and Mohammadreza Hajiesmaeili. "Therapeutic Potential of Microvesicles in Cell Therapy and Regenerative Medicine of Ocular Diseases With an Especial Focus on Mesenchymal Stem Cells-Derived Microvesicles." Frontiers in Genetics 13 (March 29, 2022). http://dx.doi.org/10.3389/fgene.2022.847679.
Повний текст джерелаАнотація:
These days, mesenchymal stem cells (MSCs), because of immunomodulatory and pro-angiogenic abilities, are known as inevitable factors in regenerative medicine and cell therapy in different diseases such as ocular disorder. Moreover, researchers have indicated that exosome possess an essential potential in the therapeutic application of ocular disease. MSC-derived exosome (MSC-DE) have been identified as efficient as MSCs for treatment of eye injuries due to their small size and rapid diffusion all over the eye. MSC-DEs easily transfer their ingredients such as miRNAs, proteins, and cytokines to the inner layer in the eye and increase the reconstruction of the injured area. Furthermore, MSC-DEs deliver their immunomodulatory cargos in inflamed sites and inhibit immune cell migration, resulting in improvement of autoimmune uveitis. Interestingly, therapeutic effects were shown only in animal models that received MSC-DE. In this review, we summarized the therapeutic potential of MSCs and MSC-DE in cell therapy and regenerative medicine of ocular diseases.
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Wang, Xiaohong, Jian Fang, and Lina Yang. "Research progress on ocular complications caused by type 2 diabetes mellitus and the function of tears and blepharons." Open Life Sciences 19, no. 1 (January 1, 2024). http://dx.doi.org/10.1515/biol-2022-0773.
Повний текст джерелаАнотація:
Abstract The purpose of this study was to explore the related research progress of ocular complications (OCs) caused by type 2 diabetes mellitus (T2DM), tear and tarsal function, and the application of deep learning (DL) in the diagnosis of diabetes and OCs caused by it, to provide reference for the prevention and control of OCs in T2DM patients. This study reviewed the pathogenesis and treatment of diabetes retinopathy, keratopathy, dry eye disease, glaucoma, and cataract, analyzed the relationship between OCs and tear function and tarsal function, and discussed the application value of DL in the diagnosis of diabetes and OCs. Diabetes retinopathy is related to hyperglycemia, angiogenic factors, oxidative stress, hypertension, hyperlipidemia, and other factors. The increase in water content in the corneal stroma leads to corneal relaxation, loss of transparency, and elasticity, and can lead to the occurrence of corneal lesions. Dry eye syndrome is related to abnormal stability of the tear film and imbalance in neural and immune regulation. Elevated intraocular pressure, inflammatory reactions, atrophy of the optic nerve head, and damage to optic nerve fibers are the causes of glaucoma. Cataract is a common eye disease in the elderly, which is a visual disorder caused by lens opacity. Oxidative stress is an important factor in the occurrence of cataracts. In clinical practice, blood sugar control, laser therapy, and drug therapy are used to control the above eye complications. The function of tear and tarsal plate will be affected by eye diseases. Retinopathy and dry eye disease caused by diabetes will cause dysfunction of tear and tarsal plate, which will affect the eye function of patients. Furthermore, DL can automatically diagnose and classify eye diseases, automatically analyze fundus images, and accurately diagnose diabetes retinopathy, macular degeneration, and other diseases by analyzing and processing eye images and data. The treatment of T2DM is difficult and prone to OCs, which seriously threatens the normal life of patients. The occurrence of OCs is closely related to abnormal tear and tarsal function. Based on DL, clinical diagnosis and treatment of diabetes and its OCs can be carried out, which has positive application value.