Occelli, LM;
Daruwalla, A;
De Silva, SR;
Winkler, PA;
Sun, K;
Pasmanter, N;
Minella, A;
... Petersen-Jones, SM; + view all
(2022)
A large animal model of RDH5-associated retinopathy recapitulates important features of the human phenotype.
Human Molecular Genetics
, 31
(8)
pp. 1263-1277.
10.1093/hmg/ddab316.
Preview |
Text
ddab316.pdf - Accepted Version Download (1MB) | Preview |
Abstract
Pathogenic variants in retinol dehydrogenase 5 (RDH5) attenuate supply of 11-cis-retinal to photoreceptors leading to a range of clinical phenotypes including night blindness due to markedly slowed rod dark adaptation and in some patients, macular atrophy. Current animal models (such as Rdh5-/- mice) fail to recapitulate the functional or degenerative phenotype. Addressing this need for a relevant animal model we present a new domestic cat model with a loss-of-function missense mutation in RDH5 (c.542G > T; p.Gly181Val). As with patients, affected cats have a marked delay in recovery of dark adaptation. Additionally, the cats develop a degeneration of the area centralis (equivalent to the human macula). This recapitulates the development of macular atrophy that is reported in a subset of patients with RDH5 mutations and is shown in this paper in 7 patients with biallelic RDH5 mutations. There is notable variability in the age at onset of the area centralis changes in the cat, with most developing changes as juveniles but some not showing changes over the first few years of age. There is similar variability in development of macular atrophy in patients and while age is a risk factor, it is hypothesized that genetic modifying loci influence disease severity, and we suspect the same is true in the cat model. This novel cat model provides opportunities to improve molecular understanding of macular atrophy and test therapeutic interventions for RDH5-associated retinopathies.
| Type: | Article |
|---|---|
| Title: | A large animal model of RDH5-associated retinopathy recapitulates important features of the human phenotype |
| Location: | England |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1093/hmg/ddab316 |
| Publisher version: | http://dx.doi.org/10.1093/hmg/ddab316 |
| Language: | English |
| Additional information: | This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. |
| Keywords: | phenotype, mutation, cats, child, dark adaptation, macula lutea, animal model, missense mutation, oxidoreductase, photoreceptors, retinal diseases, micevitamin atissue degeneration, atrophoderma maculatum |
| 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/10139111 |
Archive Staff Only
 |
View Item |
