Daich Varela, Malena;
(2024)
Clinical and Genetic Investigation of RDH12-associated Retinopathy.
Doctoral thesis (Ph.D), UCL (University College London).
Abstract
Inherited retinal diseases (IRDs) encompass a group of genetic eye disorders affecting the development or function of photoreceptors or retinal pigment epithelium (RPE) cells mainly, resulting in subnormal vision. Classification of IRDs is primarily based on phenotype, associated genes, and inheritance patterns. Retinol dehydrogenase 12 (RDH12) is a critical protein expressed in photoreceptor inner segments. Damaging variants in RDH12 can cause Leber congenital amaurosis/Early onset severe retinal dystrophy (LCA/EOSRD), a progressive and degenerative disease that leads to decreased vision and narrowed visual field from early childhood. Despite promising pre-clinical studies, there are no available treatments for RDH12-associated retinal dystrophy. One of the reasons clinical trials have not been designed yet is the paucity of robust prospective natural history data. This thesis addresses this gap by reviewing current knowledge on RDH12, vision assessment methods and the treatment landscape for LCA/EOSRD. The presented natural history study, conducted at Moorfields Eye Hospital (London, UK) from 2021 to 2023, involves novel deep phenotyping using adaptive optics scanning laser ophthalmoscopy (AOSLO), visual field modelling and analysis, and a multi-luminance navigation path. The thesis also includes novel data from individuals with RDH12-associated LCA/EOSRD from South America and patients with RDH12 differential diagnoses, such as CRB1- and RPGRIP1-retinal dystrophies. The data herein serves as a valuable resource for future clinical trial design, improving our understanding of the disease, and enabling more informed prognosis and genetic counselling.
| Type: | Thesis (Doctoral) |
|---|---|
| Qualification: | Ph.D |
| Title: | Clinical and Genetic Investigation of RDH12-associated Retinopathy |
| Language: | English |
| 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.ucl.ac.uk/id/eprint/10188744 |
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