Vision loss is a major cause of disability throughout the world. While there are effective treatments for cataracts and for preventing glaucoma, there are numerous genetic disorders that cause degeneration of cells in the retina for which no treatments currently exist. Inherited retinal diseases can be caused by recessive (loss-of function) or dominant (gain-of-function) mutations in genes expressed in photoreceptor cells or retinal pigmented epithelial (RPE) cells. Dominik Fischer, a professor of ophthalmology at the University of Oxford has been working to develop gene therapies for several of these diseases. One remarkable example of success is voretigene neparvovec which is essentially the RPE65 gene in an adeno-associated virus which is injected into the retina between the photoreceptors and the RPE cells. The RPE65 gene encodes an enzyme generates 11-cis-retinol which is necessary for visual pigment (opsin) regeneration. More than 1000 patients with loss-of-function RPE65 mutations and severe vision loss have been treated with many experiencing improvement in vision, particularly those treated in earlier stages of retinal degeneration highlighting in the importance of genetic screening and early intervention. Preclinical and clinical trials of gene therapies for other inherited retinal diseases are in progress.

LINKS

Dr. Fischer's University of Oxford profile:

https://www.ndcn.ox.ac.uk/team/dominik-fischer

Articles related to the subject matter of this episode:

https://karger.com/ore/article/66/1/179/835297/Gene-Therapy-for-Inherited-Retinal-Disease-Long

https://pmc.ncbi.nlm.nih.gov/articles/PMC8421966/pdf/atm-09-15-1278.pdf