Yang, Ye Sa;
(2021)
In-depth Advanced Phenotyping and Gene Therapy in X-linked Retinitis Pigmentosa due to Defects in RPGR.
Doctoral thesis (Ph.D), UCL (University College London).
Abstract
Defects in the RPGR (Retinitis Pigmentosa GTPase Regulator) gene account for most cases of X-linked Retinitis Pigmentosa, which follows a particularly severe clinical course typically culminating in legal blindness by the third or fourth decade. It is an untreatable condition, although the potential of gene therapy in treating inherited retinal disease holds promise. The recent success of gene therapy in the treatment of another inherited retinal disease (namely, Leber congenital amaurosis) and its approval from the United States Food and Drug Authority (FDA), European Medicines Agency (EMA) and the National Institute of Health and Care Excellence (NICE), have greatly increased anticipation. Currently, Retinitis Pigmentosa due to defects in RPGR (RPGR- RP) is the target of four clinical gene therapy trials across the world. Herein, I investigate the retinal function of a large cohort with molecularly confirmed RPGR-RP. I assessed the colour vision abilities in affected individuals using the low-vision version of the Cambridge Colour Test. Nyctalopia is a cardinal symptom of RP. I conducted a study to characterise vision- guided mobility and further refined the assessment to increase its suitability for RPGR- RP. Scotopic and mesopic microperimetry was used to characterise RPGR-RP, as well as a small number of subjects with RPGR-associated cone-rod dystrophy for comparison. Test-retest variability was analysed to help contextualise post-interventional analysis. Finally, I assessed the spatial contrast sensitivity of affected individuals under dark- adapted, as well as light-adapted conditions, and compared global metrics of contrast sensitivity with Pelli-Robson derived testing. Clinical endpoints which are sensitive, able to detect disease at an early stage and are repeatable are necessary and this study contributes to the evaluation and establishment of potential clinical endpoints for RPGR-RP.
| Type: | Thesis (Doctoral) |
|---|---|
| Qualification: | Ph.D |
| Title: | In-depth Advanced Phenotyping and Gene Therapy in X-linked Retinitis Pigmentosa due to Defects in RPGR |
| Event: | UCL |
| Language: | English |
| Additional information: | Copyright © The Author 2021. Original content in this thesis is licensed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0) Licence (https://creativecommons.org/licenses/by-nc/4.0/). Any third-party copyright material present remains the property of its respective owner(s) and is licensed under its existing terms. Access may initially be restricted at the author’s request. |
| UCL classification: | UCL 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/10134721 |
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