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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
21

Developing a patient-derived induced pluripotent stem cell model to understand the clinical and pathological changes in macular degeneration

Borooah, Shyamanga January 2016 (has links)
Late-onset retinal macular degeneration (L-ORMD) is a fully penetrant autosomal dominant macular degeneration resulting from a Ser163Arg substitution in the gene encoding the protein C1QTNF5. Clinically L-ORMD results in dark adaptation delay in the fifth decade, central visual loss in the sixth decade and further progressive visual field loss in successive decades of life. Pathologically the disease results in thick sub-retinal deposits, which have a similar composition to drusen seen in AMD, retinal pigment epithelial (RPE) loss, and neuro-retinal atrophy. The function of C1QTNF5 is incompletely understood however within the eye it is expressed most strongly by the RPE cells. An in vitro model for L-ORMD was developed using human induced pluripotent stem cells (hiPSCs) derived from patients and with stem cells from patient’s unaffected siblings used as controls. The hiPSCs were differentiated to RPE (hiPSC-RPE). L-ORMD hiPSC-RPE shared baseline characteristics with sibling control hiPSC-RPE. In order to model in vivo conditions hiPSC-RPE were grown on permeable supports in human serum enriched media. Case hiPSC-RPE cell lines were found to activate the complement pathway resulting in increased deposition of the terminal complement complex (TCC) C5b-9 when compared to control hiPSC-RPE. Using depleted serum, deposition was not affected by depletion of classical and lectin pathway components but was reduced by depletion of alternative complement pathway components. Depletion of complement components C3 and C5 abolished TCC deposition. The addition of a monoclonal antibody against C5 also reduced TCC deposition. The role of complement dysregulation in L-ORMD pathogenesis was confirmed by immunostaining of L-ORMD and age-matched control human donor retinal sections. L-ORMD retinal sections displayed increased C3d and C5b-9 deposition. Using mutant and wild type-protein generated from a bacterial expression system it was found that the mutant protein was less stable than the wild-type. In addition the wild type protein formed multimers whilst the mutant was mainly monomeric. A surface plasmon resonance (SPR) study showed an increased affinity of wild-type C1QTNF5, especially in multimeric form for complement factor H (CFH), a key regulator of the alternative complement pathway when compared to mutant protein. Taken together these studies implicate dysfunction of the alternative complement pathway in L-ORMD disease mechanism and have suggested a role for C1Q TNF5 in the extracellular matrix. The studies also show that L-ORMD and AMD share a pathogenic and clinical similarities.
22

The role of cytosolic accumulation of nuclear DNA in retinal-pigment epithelium dysfunction and age-related macular degeneration

Al Moujahed, Ahmad 24 October 2018 (has links)
Age-related Macular Degeneration (AMD) is the leading cause of irreversible vision loss among elderly people in developed countries. The non-neovascular or “dry” form of AMD accounts for 85%, whereas the neovascular or “wet” accounts for 15%, of all cases. There are no effective treatments for dry AMD mainly because the molecular mechanisms that lead to the development and progression of AMD are not fully understood. Similarly, while wet AMD is being treated with antibodies against vascular endothelial growth factor (VEGF), the underlying cause that results in the development of wet AMD remains elusive. Cytosolic accumulation of nuclear-DNA (nDNA) fragments has been found to trigger inflammation and mediate the development of multiple diseases. Because inflammation plays a pivotal role in AMD pathogenesis, we thus investigated if accumulation of cytosolic nDNA also contributes to AMD. Our data show that cytosolic nDNA is enriched in macular retinal pigment epithelium (RPE) cells of AMD patients. To study the effect of cytosolic nDNA on RPE cells, we mimicked this pathology by deleting the lysosomal endonuclease Dnase2a, which is responsible for degrading DNA fragments, using CRISPR/Cas9. This resulted in cytosolic accumulation of nDNA in cultured primary human RPE cells as well as in the RPE cell line ARPE-19. Importantly, both RPE cell types with Dnase2a loss became senescent and secreted higher levels of VGEF and pro-inflammatory cytokines compared to control. These effects were mediated by the DNA sensor STING and mTOR pathway. Additionally, similar to other senescent cells, these senescent RPE cells secreted factors that acted in a paracrine manner turning otherwise healthy RPE cells into senescent cells that start secreting VEGF as well as pro-inflammatory cytokines. Finally, we found that mice with Dnase2a deletion develop features of AMD-like retinopathy, including drusen- like deposits, thickened Bruch’s membrane, RPE damage, photoreceptor atrophy, and reduced electroretinogram. The pleiotropic downstream effects of cytosolic accumulation of nDNA in RPE cells, which are consistent with the complex AMD pathology, suggest that this phenomenon contributes to the pathogenesis of AMD and thereby opens new opportunities for therapeutic interventions. / 2020-10-24T00:00:00Z
23

Macular pigment and its contribution to visual performance in the older human eye

Patryas, Laura January 2015 (has links)
Visual function degrades with increasing age, in absence of frank disease, and affects both photopic and scotopic sensitivity. The mechanisms underlying these impairments may be related to biological (e.g., neural, optical) and environmental (e.g., smoking, dietary) factors. Recent evidence suggests that visual function may be improved following retinal carotenoid supplementation, both, in healthy and diseased eyes. Retinal carotenoids accumulate within the retina to form the macular pigment (MP) - a biomarker of antioxidant status of the eye and retinal disease risk. The objectives of this thesis were manyfold. First, the extent of vision loss (particularly scotopic sensitivity) in healthy ageing was examined. The results of this investigation showed that dark adaptation recovery slows with increasing age despite no significant change in visual acuity or fundus appearance. The technique described had excellent repeatability and correlated well with previous research. The potential link between MP and dark adaptation was also examined. The results showed that macular pigment optical density (MPOD) was correlated with a specific parameter of dark adaptation (S2) - a sensitive marker of functional degradation in normal ageing and retinal disease. The main part of this thesis sought to investigate the effect of MP augmentation on visual function in a large group of observers aged between 50 and 90 years old. The baseline data from this clinical trial revealed very interesting findings with regards to unhealthy lifestyle behaviours, health status and statin use. Subjects taking statins were identified (n = 25) and matched with 25 participants not using statins for age and body mass index. It was found that statin users had a higher proportion of males, higher prevalence of current smoking status and poorer general health (e.g. hypertension, high cholesterol and heart disease). Statin users also had significantly reduced MPOD, prolonged photostress recovery time, and deficits in a number of dark adaptation parameters. In a separate analysis of the whole group (n= 74, mean age 65.51), smokers were found to have reduced MPOD, slower S2, higher prevalence of high cholesterol and lower fruit and vegetable intake. MPOD was also reduced among obese subjects. The impact of MP augmentation on visual function in normal older subjects was assessed (n = 74, mean age 65.51) in a 12 month, randomized, double-blind, placebo-controlled study. Active formulation consisted of 20 mg lutein combined with vitamins and minerals. Data were collected at baseline, 6 months and 12 months. The results showed that, despite a 24% MPOD increase in the active group, there were no significant differences between the two groups over the three visits for any of the visual parameters. Given the increasing size of the older adult population in developed countries, research aimed at slowing or reversing age-related declines in vision is much needed both from an economical and psycho-social perspective. The results of the studies presented in this thesis show that lifestyle, health status and certain medications can adversely affect visual function in normal ageing. MP augmentation, however, had no effect on visual function. Further research is warranted, particularly paying close attention to subjects engaging in several unhealthy lifestyle/dietary behaviours, statin users and those with low MPOD and suboptimal visual function.
24

Aging and human macular pigment density : appended with translations from the work of Max Schultze and Ewald Hering

Werner, John S., Donnelly, Seaneen K., Kliegl, Reinhold January 1987 (has links)
The optical density of human macular pigment was measured for 50 observers ranging in age from 10 to 90 years. The psychophysical method required adjusting the radiance of a 1°, monochromatic light (400–550 nm) to minimize flicker (15 Hz) when presented in counterphase with a 460 nm standard. This test stimulus was presented superimposed on a broad-band, short-wave background. Macular pigment density was determined by comparing sensitivity under these conditions for the fovea, where macular pigment is maximal, and 5° temporally. This difference spectrum, measured for 12 observers, matched Wyszecki and Stiles's standard density spectrum for macular pigment. To study variation in macular pigment density for a larger group of observers, measurements were made at only selected spectral points (460, 500 and 550 nm). The mean optical density at 460 nm for the complete sample of 50 subjects was 0.39. Substantial individual differences in density were found (ca. 0.10–0.80), but this variation was not systematically related to age.
25

Activation of microglia in ageing retina and in age-related macular degeneration and their role in RPE degeneration

Devarajan, Gayathri January 2012 (has links)
No description available.
26

Spectral reflectance imaging of the ocular fundus using a scanning laser ophthalmoscope

Kirkpatrick, James Nigel Pollock January 1997 (has links)
An investigation of the spectral reflectance of the fundus in normals and patients with common eye diseases was carried out using a multi wavelength scanning laser ophthalmoscope (SLO). With a knowledge of the spectral properties of the principal ocular pigments in the fundus, the appearance of the retina and choroid is predictable in normal subjects. The optic disc has a characteristic dark appearance when viewed with the SLO, and reasons for this may include a filtering effect of the confocal aperture to reduce the return of scattered light to the detector. In patients with macular exudates these features have a high reflectance in green-yellow light. An image processing method has been developed to quantify exudates and this was applied to SLO images and digitised colour slides of the same patients. Results show similar performance of processing in both image types with high accuracy (90% sensitivity for 95% specificity). A similar experiment was carried out on patients with macular drusen. These structures are of lower intensity than exudates and may have less well-defined borders. Again performance of the image processing methods showed broadly similar performance when comparing SLO images and digitised colour slides (60 to 68% sensitivity for 95% specificity). A study was carried out to assess the ability of the SLO to image the fundus in patients with cataract using a range of wavelengths. In conclusion the SLO offers the ability to image the fundus at selected wavelengths to enhance the desired features under investigation. As a fundus camera, used to generate digital images, it is unlikely to offer significant improvements over commercially available digital imaging CCD cameras. However, the SLO has properties which are likely to make it an ideal instrument for reflectometry, angiography and fundus topography. These applications are discussed in the final chapter.
27

Chemical and photic damage to DNA as pathogenetic mechanisms in the aetiology of macular degeneration of the eye

Patton, William P. January 1998 (has links)
No description available.
28

Protective effect of statin use in the progression of dry to exudative age-related macular degeneration

Nettune, Gregory. January 2006 (has links)
Thesis (Ph.D.)--The University of Texas Southwestern Medical Center at Dallas, 2006. / Embargoed. Vita. Bibliography.
29

Reading performance in visual impairment

Bowers, Alexandra Rae January 1998 (has links)
No description available.
30

A novel association between serum bilirubin levels and age-related macular degeneration

Akella, Sudheer 22 January 2016 (has links)
The purpose of this study is to examine the association between serum bilirubin and the development of age-related macular degeneration (AMD). The study design includes the utilization of a USA-nationally representative population based cross-sectional study in the National Health and Nutrition Examination Survey: specifically, the NHANES III and continuous NHANES from years 2005-2008. 15,501 survey participants from the NHANES studies chosen for this analysis were interviewed for demographic, behavioral, and medical information, put through a comprehensive medical examination segment, and a laboratory analysis portion. The 15,501 participants were chosen based on their age (40 and above) and the presence of fundus photographs. Fundus photographs were graded using standardized protocol to diagnose early and later AMD, which were combined to form the outcome "AMD" in a binary variable. Serum bilirubin levels were measured using spectrophotometry. Of the 15,501 participants in the study, 1305 (8.9%) were diagnosed with AMD. In a multivariate logistic regression adjusted for age, sex, smoking status, race, and serum C-reactive protein (CRP) levels, bilirubin was significantly associated with AMD (odds ratio, 0.728; confidence interval, 0.547-0.969; P value, 0.0296). The findings of this study indicate that the antioxidative effects of bilirubin may play protective role in the pathology of AMD.

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