Lynch, Aisling;
(2018)
Investigating the influence of retinal pigment epithelium on retinal function with a view to studying RPE cell transplantation.
Doctoral thesis (Ph.D), UCL (University College London).
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Abstract
Age-related macular degeneration (AMD) is a debilitating disease and the leading cause of blindness in the developed world. It is a disease of the retinal pigment epithelium (RPE), the support cells for rods and cones. Currently there are no approved methods of treating the failing RPE, however, RPE transplantation is proving to be a promising therapy. The royal college of surgeons (RCS) rat has been extensively studied as a model for RPE transplantation, although, it does not model RPE death, as RPE remain intact in this disease model. In this thesis, I examine two alternative mouse models and their suitably for RPE transplantation. The first model uses sodium iodate to selectively kill off the RPE, which results in rapid retinal degeneration. Chemically removing the RPE frees Burch’s membrane for donor RPE attachment. It was discovered that this model results in severe loss of outer-retinal photoreceptor function and function was unable to be restored with human embryonic stem cell-derived RPE (hESC-RPE) transplantation. The second model is the rd12 mouse, which has a mutation in rpe65, arresting the visual cycle. Thus, improvements in visual function would be specific to the visual cycle. This model, showed slow retinal degeneration and an ability for retinal function rescue with synthetic chromophore and hESC-RPE transplantation, though, no surviving grafted hESC-RPE were found in the retina. This study also examines the effects of RPE on melanopsin function. Melanopsin labelling and function was significantly reduced in rd12 mice. It was shown that supplementing chromophore significantly restored the intrinsic pupillary light reflex (iPLR) in rd12 and that this requires retina attached to the iris/ciliary body. Restoring rpe65 gene function improves melanopsin function when the gene is placed subretinally and expressed by the RPE and no effect is seen when the gene is placed intravitreally.
| Type: | Thesis (Doctoral) |
|---|---|
| Qualification: | Ph.D |
| Title: | Investigating the influence of retinal pigment epithelium on retinal function with a view to studying RPE cell transplantation |
| Event: | UCL (University College London) |
| Open access status: | An open access version is available from UCL Discovery |
| Language: | English |
| UCL classification: | UCL > Provost and Vice Provost Offices UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Institute of Ophthalmology |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10047582 |
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