Athanasiou, D;
Aguila, M;
Bellingham, J;
Li, W;
McCulley, C;
Reeves, PJ;
Cheetham, ME;
(2018)
The molecular and cellular basis of rhodopsin retinitis pigmentosa reveals potential strategies for therapy.
Progress in Retinal and Eye Research
, 62
pp. 1-23.
10.1016/j.preteyeres.2017.10.002.
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Abstract
Inherited mutations in the rod visual pigment, rhodopsin, cause the degenerative blinding condition, retinitis pigmentosa (RP). Over 150 different mutations in rhodopsin have been identified and, collectively, they are the most common cause of autosomal dominant RP (adRP). Mutations in rhodopsin are also associated with dominant congenital stationary night blindness (adCSNB) and, less frequently, recessive RP (arRP). Recessive RP is usually associated with loss of rhodopsin function, whereas the dominant conditions are a consequence of gain of function and/or dominant negative activity. The in-depth characterisation of many rhodopsin mutations has revealed that there are distinct consequences on the protein structure and function associated with different mutations. Here we categorise rhodopsin mutations into seven discrete classes; with defects ranging from misfolding and disruption of proteostasis, through mislocalisation and disrupted intracellular traffic to instability and altered function. Rhodopsin adRP offers a unique paradigm to understand how disturbances in photoreceptor homeostasis can lead to neuronal cell death. Furthermore, a wide range of therapies have been tested in rhodopsin RP, from gene therapy and gene editing to pharmacological interventions. The understanding of the disease mechanisms associated with rhodopsin RP and the development of targeted therapies offer the potential of treatment for this currently untreatable neurodegeneration.
| Type: | Article |
|---|---|
| Title: | The molecular and cellular basis of rhodopsin retinitis pigmentosa reveals potential strategies for therapy |
| Location: | England |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.preteyeres.2017.10.002 |
| Publisher version: | https://doi.org/10.1016/j.preteyeres.2017.10.002 |
| Language: | English |
| Additional information: | © 2017 Published by Elsevier Ltd. This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. |
| Keywords: | CRISPR, Endocytosis, GPCR, Mutation, Neurodegeneration, Protein misfolding, Protein traffic, Proteostasis, Retinal dystrophy, Rhodopsin, Therapy |
| 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/10025810 |
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