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1

Karwatowski, Wojciech Stefan Stanislaw. "Bruch's membrane and its collagen". Thesis, University of Bristol, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.361162.

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2

Lee, Yunhee. "Characterisation and modulation of the gelatinase system of human Bruch's membrane". Thesis, King's College London (University of London), 2012. https://kclpure.kcl.ac.uk/portal/en/theses/characterisation-and-modulation-of-the-gelatinase-system-of-human-bruchs-membrane(013f751e-04af-44a8-a866-2eec03998309).html.

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Ageing of Bruch’s membrane is associated with structural and functional deterioration. Accumulation of normal and abnormal collagen in ageing Bruch’s has led to the hypothesis of diminished matrix degradation mediated normally by a family of protease enzymes called the matrix metalloproteinases (MMPs). Underlying mechanisms leading to diminished MMP activity in ageing Bruch’s remain unknown but functional changes of diminished transport are well documented. Ageing remains the biggest risk factor in AMD with nearly 30% of all individuals reaching the age of 85 years showing some loss of central vision. In the present thesis, the gelatinase system (constituting MMPs 2&9) has been examined resulting in the identification and characterisation of three additional high molecular weight species termed HMW 1&2 and a large macromolecular weight MMP complex (LMMC). HMW1&2 were shown to be covalently bonded homo-and/or hetero- polymers of pro-MMPs 2&9. HMW species in effect sequester pro-MMPs 2&9 reducing the pool available for activation and the age-related increase in HMW species is expected to augment this reduction. In Bruch’s membrane from donors with AMD, levels of HMW1&2 were considerably elevated (p<0.05) with a concomitant reduction in the amount of active MMPs 2&9 (p<0.05). The reduction in activated MMP species therefore underlies the reduced degradative capacity of Bruch’s in these patients. Elution studies demonstrated the existence of a free-bound equilibrium for the gelatinases with the bound forms being retained by hydrophobic, ionic or metal mediated interactions. Since divalent metal ions are deposited in Bruch’s of AMD donors, metal chelation was assessed as a possible means of inducing MMP release. Metal chelation with EGTA resulted in the release of active forms of MMP2 and significantly improved the fluid transport properties of the membrane (p<0.005).
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3

Zayas-Santiago, Astrid, Samuel D. Cross, James B. Stanton, Alan D. Marmorstein e Lihua Y. Marmorstein. "Mutant Fibulin-3 Causes Proteoglycan Accumulation and Impaired Diffusion Across Bruch's Membrane". ASSOC RESEARCH VISION OPHTHALMOLOGY INC, 2017. http://hdl.handle.net/10150/624956.

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PURPOSE. The mutation R345W in EFEMP1 (fibulin-3) causes macular degeneration. This study sought to determine whether proteoglycan content and diffusion across Bruch's membrane are altered in Efemp1(ki/ki) mice carrying this mutation or in Efemp1(-/-) mice. METHODS. Proteoglycans in mouse Bruch's membranes were stained with Cupromeronic Blue (CB). Heparan sulfated proteoglycan (HSPG) and chondroitin/dermatan sulfate proteoglycan (C/DSPG) distributions were visualized following treatments with chondroitinase ABC (C-ABC) or nitrous acid. Total sulfated glycosaminoglycans (sGAGs) in Bruch's membrane/choroid (BrM/Ch) were measured with dimethylmethylene blue (DMMB). Matrix metalloprotease (MMP)-2, MMP-9, and tissue inhibitor of metalloproteinase (TIMP)-3 were examined by immunofluorescence and quantified using Image J. Molecules with different Stokes radius (R-s) were allowed simultaneously to diffuse through mouse BrM/Ch mounted in a modified Ussing chamber. Samples were quantified using gel exclusion chromatography. RESULTS. HSPGs and C/DSPGs were markedly increased in Efemp1(ki/ki) Bruch's membrane, and MMP-2 and MMP-9 were decreased, but TIMP-3 was increased. Diffusion across Efemp1(ki/ki) Bruch's membrane was impaired. In contrast, the proteoglycan amount in Efemp1(-/-) Bruch's membrane was not significantly different, but the size of proteoglycans was much larger. MMP-2, MMP-3, and TIMP-3 levels were similar to that of Efemp1(+/+) mice, but they were localized diffusely in retinal pigment epithelium (RPE) cells instead of Bruch's membrane. Diffusion across Efemp1(-/-) Bruch's membrane was enhanced. CONCLUSIONS. Mutant fibulin-3 causes proteoglycan accumulation, reduction of MMP-2 and MMP-9, but increase of TIMP-3, and impairs diffusion across Bruch's membrane. Fibulin-3 ablation results in altered sizes of proteoglycans, altered distributions of MMP-2, MMP-9, and TIMP-3, and enhances diffusion across Bruch's membrane.
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4

Moore, David Jonathan. "An investigation of the permeability of Bruch's membrane and its variation with age". Thesis, King's College London (University of London), 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.338867.

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5

Haneef, Atikah Shahid. "Fabrication of novel cytocompatible membranes for ocular application, concentrating in particular on age-related macular degeneration (AMD)". Thesis, University of Manchester, 2014. https://www.research.manchester.ac.uk/portal/en/theses/fabrication-of-novel-cytocompatible-membranes-for-ocular-application-concentrating-in-particular-on-agerelated-macular-degeneration-amd(7d1ace68-09d8-4c64-83e7-3ede1e2f52e1).html.

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The aims of this research were to investigate polymer fibre morphology, overall mat morphology, mechanical properties and general handling of the mats, and ideal mat thickness in order to fabricate a suitable substrate for potential use in cell transplantation for application as a permanent substrate for the treatment of dry age-related macular degeneration (AMD). Polystyrene (PS), poly(ethylene terephthalate) (PET) and polyurethane (PU) were electrospun to ascertain the ideal electrospinning parameters to reproducibly obtain fibres to construct a mat as a potential candidate for a replacement Bruch’s membrane (BM). After identifying the ideal spinning parameters, mats were fabricated, their fibre morphology, overall mat morphology, and handling during processing were examined. This allowed the shortlisting of PS and PET substrates, which were suitable to be taken forward for further testing and cell culture. PU was found to be unsuitable as it had a tendency to become entwined and stick to itself, which would destroy the gross mat morphology. Therefore PU was excluded from further testing. Further handling, both quantitative and qualitative, and thickness and porosity were tested for PS and PET mats. Electrospun PET demonstrated greater handling and durability properties compared to PS mats, which were more fragile. PET was able to withstand twisting, folding, and rolling, whereas PS could not undergo twisting and fell apart. PS mats were thicker and more porous compared to PET mats, which was attributed to the widely spaced placement of the larger PS fibres and the fluffy gross morphology of the PS mats, in comparison to the closer fibre placement of the smaller PET mats which had a smooth gross mat morphology. Considering this, PS mats were compressed and thickness and porosity was reduced, while maintaining its fibrous structure. However the compressed PS mats became extremely fragile and could not withstand much handling. Although PET mats were thinner than PS mats, it did not match the native BM thickness and so experiments in varying collection time during electrospinning to match the native BM thickness were undertaken. Tensile tests, thickness and porosity measurements showed that PET tensile properties, thickness, and porosity reduced with reduced collection time. For the purposes of surface treatment and cell culture, uncompressed mats collected for 60 minutes were used since sufficient PS fibres were able to be collected to form a mat that was able to withstand processing at this collection time. Effect of UV/ozone surface treatment was tested for both PS and PET mats. Treatment of both substrate types affected protein adsorption, with evidence of aminolysis observed on PET substrates. Short-term initial growth and survival of retinal pigment epithelial cells (RPE cells) on electrospun, surface oxidised PS and PET was investigated. Untreated PS did not support cell proliferation and although treated PS did, the resultant RPE cell morphology was undesirable, therefore was not taken forward to long term cell culture. Treated and untreated PET supported cell proliferation, and was taken forward to the long term culture study, where cells exhibited the desired monolayer morphology. In this work it has been demonstrated that electrospun PET may potentially be a suitable candidate as cell carrier substrate for subsequent implantation in application towards AMD treatment.
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6

Duvall-Young, Josephine. "New concepts in the pathophysiology of macular disease : morphological responses in the choriocapillaris and Bruch's membrane". Thesis, University of Edinburgh, 1988. http://hdl.handle.net/1842/18853.

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7

Starita, Carla. "An investigation of the site of resistance to fluid transport within Bruch's membrane and changes with age". Thesis, King's College London (University of London), 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.250686.

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8

Ahir, Alpa. "An investigation of matrix metalloproteinases derived from retinal pigment epithelial cells and their influence on fluid movement through Bruch's membrane". Thesis, King's College London (University of London), 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.274921.

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9

Hodgetts, Andrea. "An investigation of the changes in fibre and matrix components of human Bruch's membrane as a function of age and their implications for movement of fluids". Thesis, King's College London (University of London), 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.246304.

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10

Shadforth, Audra M. "Development of a cultured tissue substitute to repair the ageing retina". Thesis, Queensland University of Technology, 2015. https://eprints.qut.edu.au/90058/12/Audra_Shadforth_Thesis.pdf.

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This project provides a foundation for the use of silk membranes in a tissue engineered therapy for the treatment of devastating retinal diseases such as age-related macular degeneration. The three-dimensional tissue model described in this thesis has great potential for use in basic research of retinal pathologies, and the potential to be implemented into clinical approaches after appropriate refinement.
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11

Cherepanoff, Svetlana. "Age-related macular degeneration: histopathological and serum autoantibody studies". University of Sydney, 2008. http://hdl.handle.net/2123/2464.

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Doctor of Philosophy (PhD)
BACKGROUND: The accumulation of abnormal extracellular deposits beneath the retinal pigment epithelium characterises the pathology of early age-related macular degeneration. However, the histopathological threshold at which age-related changes become early AMD is not defined, and the effect of each of the deposits (basal laminar deposit and membranous debris) on disease progression is poorly understood. Evidence suggests that macrophages play a key role in the development of AMD lesions, but the influence of basal laminar deposit (BLamD) and membranous debris on the recruitment and programming of local macrophages has not been explored. Although evidence also suggests that inflammation and innate immunity are involved in AMD, the significance of anti-retinal autoantibodies to disesase pathogenesis is not known. AIMS: (i) To determine the histopathological threshold that distinguishes normal ageing from early AMD; (ii) to determine the influence of BLamD and membranous debris on disease progression; (iii) to examine whether distinct early AMD phenotypes exist based on clinicopathological evidence; (iv) to determine the histopathological context in which Bruch’s membrane macrophages first found; (v) to examine the relationship between Bruch’s membrane macrophages and subclinical neovascularisation; (vi) to determine if the progressive accumulation of BLamD and membranous debris alters the immunophenotype of Bruch’s membrane macrophages and/or resident choroidal macrophages; (vii) to determine if the anti-retinal autoantibody profile differs significantly between normal individuals and those with early AMD, neovascular AMD or geographic atrophy; (viii) to examine whether baseline anti-retinal autoantibodies can predict progression to advanced AMD in individuals with early AMD; and (ix) to examine whether baseline anti-retinal autoantibodies can predict vision loss in individuals with neovascular AMD. METHODS:Clinicopathological studies were performed to correlate progressive accumulation of BLamD and membranous debris to fundus characteristics and visual acuity, as well as to sub-macular Bruch’s membrane macrophage count. Immunohistochemical studies were perfomed to determine whether the presence of BLamD and membranous debris altered the programming of Bruch’s membrane or resident choroidal macrophages. The presence of serum anti-retinal autoantibodies was determined by western blotting, and the association with disease progression examined in early and neovascular AMD. RESULTS: The presence of both basal linear deposit (BLinD) and a continuous layer of BLamD represents threshold early AMD histopathologically, which was seen clinically as a normal fundus in the majority of cases. Membranous debris accumulation appeared to influence the pathway of progression from early AMD to advanced AMD. Bruch’s membrane macrophages were first noted when a continuous layer of BLamD and clinical evidence of early AMD were present, and increased with the amount of membranous debris in eyes with thin BLamD. Eyes with subclinical CNV had high macrophage counts and there was some evidence of altered resident choroidal macrophage programming in the presence of BLamD and membranous debris. Serum anti-retinal autoantibodies were found in a higher proportion of early AMD participants compared with both controls and participants with neovascular AMD, and in a higher proportion of individuals with atrophic AMD compared to those with neovascular AMD. The presence of baseline anti-retinal autoantibodies in participants with early AMD was not associated with progression to advanced AMD. Participants with neovascular AMD lost more vision over 24 months if they had IgG autoantibodies at baseline compared to autoantibody negative participants. CONCLUSIONS: The finding that eyes with threshold early AMD appear clinically normal underscores the need to utilise more sophisticated tests to enable earlier disease detection. Clinicopathological evidence suggests two distinct early AMD phenotypes, which follow two pathways of AMD progression. Macrophage recruitment and programming may be altered by the presence of BLamD and membranous debris, highlighting the need to further characterise the biology of human resident choroidal macropahges. Anti-retinal autoantibodies can be found in both control and AMD sera, and future approaches that allow the examination of subtle changes in complex repertoires will determine whether they are involved in AMD disease pathogenesis.
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12

Ivert, Lena. "Interactions between neural retina, retinal epithelium and choroid /". Stockholm : Section of ophthalmology and vision, Department of clinical neuroscience, Karolinska institutet, 2006. http://diss.kib.ki.se/2006/91-7140-797-9/.

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13

Zeng, Ziqian. "Fabrication and Development of a PCL Electrospun Fiber - Keratin Aerogel Scaffold to Mimic Bruch’s Membrane for the Study of Age-related Macular Degeneration". Miami University / OhioLINK, 2017. http://rave.ohiolink.edu/etdc/view?acc_num=miami1502103996594191.

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14

Kabbara, Sami. "Comparing Optical Coherence Tomography Radial and Cube Scan Patterns for Measuring Bruch’s Membrane Opening Minimum Rim Width (BMO-MRW) in Glaucoma and Healthy Eyes: Cross-sectional and Longitudinal Analysis". Thesis, The University of Arizona, 2018. http://hdl.handle.net/10150/627199.

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A Thesis submitted to The University of Arizona College of Medicine - Phoenix in partial fulfillment of the requirements for the Degree of Doctor of Medicine.
Background and Significance: Spectral Domain-Optical Coherence Tomography (OCT) is one of the most widely used imaging modality in Ophthalmology. It utilizes light waves to visualize the various layers of the retina. The OCT machines offer two different scan patterns, the circular and the cube scan patters. It is important to compare these scan pattern to see if any discrepancy exist in quantifying retinal indices. One of the newer indices is the Bruch’s membrane opening minimum rim width (BMO-MRW), which is the minimum distance between from the BMO to the inner limiting membrane (ILM). The BMO-MRW is being used in the diagnosis of glaucoma. Hypothesis: To compare the cube and radial scan patterns of the SD-OCT for quantifying the BMO-MRW. We hypothesis that there might be some differences between the two scan patterns.
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15

Richert, Elisabeth [Verfasser]. "Wirkung schonender Laserverfahren auf den Komplex aus retinalem Pigmentepithel, Bruch´scher Membran und Choroidea - mögliche Therapieoption der frühen altersabhängigen Makuladegeneration / Elisabeth Richert". Kiel : Universitätsbibliothek Kiel, 2017. http://d-nb.info/1133074014/34.

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16

Gmeiner, Jonas Maximilian David [Verfasser], Christian [Akademischer Betreuer] Mardin e Christian [Gutachter] Mardin. "Vergleich von Bruch-Membran basierter Minimaler Randsaumweite und Peripapillärer Nervenfaserschichtdicke in der Frühdiagnostik von Glaukomen / Jonas Maximilian David Gmeiner ; Gutachter: Christian Mardin ; Betreuer: Christian Mardin". Erlangen : Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), 2020. http://d-nb.info/1214443451/34.

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17

"Deleterious effect of A2E in human RPE cells and Bruch's membrane". NORTHERN ILLINOIS UNIVERSITY, 2009. http://pqdtopen.proquest.com/#viewpdf?dispub=1460974.

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18

Lundkvist, Stefan. "OCT (Optical Coherense Tomography) : Teknik och tillämpning". Thesis, 2013. http://urn.kb.se/resolve?urn=urn:nbn:se:ltu:diva-52886.

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Before year 1895, the doctors could only make a probable diagnosis based on what the patient could tell and it was hurt and there was no discernable change to the outside of the body. With X-ray, it was possible to see inside the patient without first cutting it, you can say that the X-ray was the starting point for diagnostic imaging.The further development of X-ray gave CT (Computed Tomography), where X-ray tubes and detectors rotate around the patient while the patient table moves. Besides CT also developed MRI (Magnetic Resonance Imaging), PET (Positron Emission Tomography) and Ultrasound. Common to these methods is that the produced 3D images.In 1990 a completely new approach for diagnostic imaging, OCT (optical coherence tomography), by measuring the phase shift and the intensity of reflected light, it provides real-time and non-destructive measurements (in vivo) a resolution of 1 to 15 microns, much higher than all other standard imaging techniques. You could say that OCT machine can be compared to ultrasound, which uses the reflection of sound waves to interpretation.The first OCT machines were of type TD (Time Domain), these had low resolution and low scanning speed. In 2005 came the SD-OCT, they had higher resolution and scanning speed, SD stands for spectral domain, SD-OCT is sometimes called FD-OCT as Fourier transformed signals and operating in the frequency domain.The development of OCT machines are only in their infancy, resolution, scanning speed and accuracy will increase all the time, this allows new uses and ways to diagnose developed. OCT can be used in such Oncology, MSD (Musculoskeletal disorders), cardiovascular medicine, teeth, nerves, but the largest field is the eye and then the back of the eye called the retina (retina).This thesis is limited to the eye, the purpose is to provide input to those who are likely to purchase an OCT-machine, but also show the measurement data OCT-machines are performing and how to use the OCT-machine more than to see age-related macular degeneration. Another aim is to increase understanding of the physics behind an OCT-machine for ease of understanding the output given.The manufacture/model that have selected for evaluation are Zeiss Cirrus 4000, Topcon 3D OCT-2000 and Heidelberg Spectralis, the reason is that there are only these three on the Swedish market and all are SD-OCT. The way to evaluate OCT-machines is to scan performance and what the various analysis programs can handle. Furthermore, each OCT-machine scans the macula and optic disk on a experimental person/ reference eye, in order to get the output of the precision, or if you want to call it repeatability, which is very important if one wants to follow a solitary disease course.The conclusion of this thesis is to OCT machines are quite similar. When it comes to ease of use when doing scans is the Cirrus is lightened by the use of the extra screen where you always look eye (iris camera), which makes it easy to adjust the sharpness and position of the mouse buttons. Topcon and Heidelberg is not difficult to use but requires more experience of the person making the OCT scans. Most measurement functions in the analysis program is Topcon and Heidelberg and best accuracy/repeatability is Heidelberg, both the macula and RFNL.OCT machine is a good tool to use on the anterior segment, but in the case the precision allows the precision used to monitor RNFL thickness changes in those with glaucoma.

Validerat; 20131029 (global_studentproject_submitter)

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