Long-term vitamin A supplementation in a preclinical mouse model for RhoD190N-associated retinitis pigmentosa.

Abstract

Retinitis pigmentosa (RP) is caused by one of many possible gene mutations. The National Institutes of Health recommends high daily doses of vitamin A palmitate for RP patients. There is a critical knowledge gap surrounding the therapeutic applicability of vitamin A to patients with the different subtypes of the disease. Here, we present a case report of a patient with RP caused by a p.D190N mutation in Rhodopsin (RHO) associated with abnormally high quantitative autofluorescence values after long-term vitamin A supplementation. We investigated the effects of vitamin A treatment strategy on RP caused by the p.D190N mutation in RHO by exposing Rhodopsin p.D190N (RhoD190N/+) and wild-type (WT) mice to experimental vitamin A-supplemented and standard control diets. The patient's case suggests that the vitamin A treatment strategy should be further studied to determine its effect on RP caused by p.D190N mutation in RHO and other mutations. Our mouse experiments revealed that RhoD190N/+ mice on the vitamin A diet exhibited higher levels of autofluorescence and lipofuscin metabolites compared to WT mice on the same diet and isogenic controls on the standard control diet. Vitamin A supplementation diminished photoreceptor function in RhoD190N/+ mice while preserving cone response in WT mice. Our findings highlight the importance of more investigations into the efficacy of clinical treatments like vitamin A for patients with certain genetic subtypes of disease and of genotyping in the precision care of inherited retinal degenerations.

• Authors: Xuan Cui, Hye Jin Kim, Chia-Hua Cheng, Laura A Jenny, Jose Ronaldo Lima de Carvalho, Ya-Ju Chang, Yang Kong, Chun-Wei Hsu, I-Wen Huang, Sara D Ragi, Chyuan-Sheng Lin, Xiaorong Li, Janet R Sparrow, Stephen H Tsang
• Journal: Human molecular genetics (Hum Mol Genet) Vol. 31 Issue 14 Pg. 2438-2451 (07 21 2022) ISSN: 1460-2083 [Electronic] England
• PMID: 35195241 (Publication Type: Case Reports, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © The Author(s) 2022. Published by Oxford University Press. All rights reserved. For Permissions, please email: [email protected].

Chemical References

• Vitamin A
• Rhodopsin

Topics

• Animals
• Dietary Supplements
• Mice
• Mutation
• Retinal Degeneration (genetics)
• Retinitis Pigmentosa (drug therapy, genetics, metabolism)
• Rhodopsin (genetics, metabolism)
• Vitamin A