Dynamic features of the mature retinal pigment epithelium.
Doctoral thesis, UCL (University College London).
The retinal pigment epithelium (RPE) is a monolayer of cells that are vital for visual function and play a key role in the maintenance of the photoreceptors. Within RPE cells are melanin granules which absorb stray light and minimise scatter within the eye, therefore, protecting the RPE from damage. Albinos lack this protective capacity of melanin as a result of mutations of the tyrosinase gene. The first half of this thesis investigates heterogeneity within the RPE in both pigmentation phenotypes. Furthermore, the effect of ageing on the RPE is examined. Immunohistochemistry highlighted the molecular heterogeneity of the RPE and how this varies with pigmentation phenotype. In aged animals, SEM revealed abnormalities occurring within the photoreceptor outer segments of albinos, while ERGs and QRT-PCR illustrated that albinos show the signs of an age-related decline in visual function much sooner than pigmented animals. These studies revealed that in the outer retina, albinism is a progressive disease and not simply a congenital abnormality. The second half of this thesis investigates migration and proliferation of RPE cells in healthy pigmented animals. Using BrdU and DiI it was established that individual RPE cells have the ability to migrate. In addition, the effect of inducing lesions in different retinal locations was studied to determine whether this affects the response of RPE cells to the damaged area. The results conveyed that a single unilateral lesion in the RPE caused an upregulation of proliferating cells not only in the lasered eye, but also the contralateral unlasered eye in a quadrant specific manner. An additional experiment investigated the effect of treating rats with Glatiramer Acetate and found that it elevates levels of cell proliferation in the RPE of treated animals. Together, the data presented in this thesis demonstrate that the mature RPE is a dynamic heterogeneous epithelial cell layer.
|Title:||Dynamic features of the mature retinal pigment epithelium|
|UCL classification:||UCL > School of Life and Medical Sciences > Faculty of Brain Sciences > Institute of Ophthalmology > Institute of Ophthalmology - Visual Neuroscience|
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