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Rhodopsin-associated retinal dystrophy: Disease mechanisms and therapeutic strategies

Rhodopsin is a light-sensitive G protein-coupled receptor that initiates the phototransduction cascade in rod photoreceptors. Mutations in the rhodopsin-encoding gene RHO are the leading cause of autosomal dominant retinitis pigmentosa (ADRP). To date, more than 200 mutations have been identified in...

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Autores principales: Zhen, Fangyuan, Zou, Tongdan, Wang, Ting, Zhou, Yongwei, Dong, Shuqian, Zhang, Houbin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10106759/
https://www.ncbi.nlm.nih.gov/pubmed/37077319
http://dx.doi.org/10.3389/fnins.2023.1132179
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author Zhen, Fangyuan
Zou, Tongdan
Wang, Ting
Zhou, Yongwei
Dong, Shuqian
Zhang, Houbin
author_facet Zhen, Fangyuan
Zou, Tongdan
Wang, Ting
Zhou, Yongwei
Dong, Shuqian
Zhang, Houbin
author_sort Zhen, Fangyuan
collection PubMed
description Rhodopsin is a light-sensitive G protein-coupled receptor that initiates the phototransduction cascade in rod photoreceptors. Mutations in the rhodopsin-encoding gene RHO are the leading cause of autosomal dominant retinitis pigmentosa (ADRP). To date, more than 200 mutations have been identified in RHO. The high allelic heterogeneity of RHO mutations suggests complicated pathogenic mechanisms. Here, we discuss representative RHO mutations as examples to briefly summarize the mechanisms underlying rhodopsin-related retinal dystrophy, which include but are not limited to endoplasmic reticulum stress and calcium ion dysregulation resulting from protein misfolding, mistrafficking, and malfunction. Based on recent advances in our understanding of disease mechanisms, various treatment methods, including adaptation, whole-eye electrical stimulation, and small molecular compounds, have been developed. Additionally, innovative therapeutic treatment strategies, such as antisense oligonucleotide therapy, gene therapy, optogenetic therapy, and stem cell therapy, have achieved promising outcomes in preclinical disease models of rhodopsin mutations. Successful translation of these treatment strategies may effectively ameliorate, prevent or rescue vision loss related to rhodopsin mutations.
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spelling pubmed-101067592023-04-18 Rhodopsin-associated retinal dystrophy: Disease mechanisms and therapeutic strategies Zhen, Fangyuan Zou, Tongdan Wang, Ting Zhou, Yongwei Dong, Shuqian Zhang, Houbin Front Neurosci Neuroscience Rhodopsin is a light-sensitive G protein-coupled receptor that initiates the phototransduction cascade in rod photoreceptors. Mutations in the rhodopsin-encoding gene RHO are the leading cause of autosomal dominant retinitis pigmentosa (ADRP). To date, more than 200 mutations have been identified in RHO. The high allelic heterogeneity of RHO mutations suggests complicated pathogenic mechanisms. Here, we discuss representative RHO mutations as examples to briefly summarize the mechanisms underlying rhodopsin-related retinal dystrophy, which include but are not limited to endoplasmic reticulum stress and calcium ion dysregulation resulting from protein misfolding, mistrafficking, and malfunction. Based on recent advances in our understanding of disease mechanisms, various treatment methods, including adaptation, whole-eye electrical stimulation, and small molecular compounds, have been developed. Additionally, innovative therapeutic treatment strategies, such as antisense oligonucleotide therapy, gene therapy, optogenetic therapy, and stem cell therapy, have achieved promising outcomes in preclinical disease models of rhodopsin mutations. Successful translation of these treatment strategies may effectively ameliorate, prevent or rescue vision loss related to rhodopsin mutations. Frontiers Media S.A. 2023-04-03 /pmc/articles/PMC10106759/ /pubmed/37077319 http://dx.doi.org/10.3389/fnins.2023.1132179 Text en Copyright © 2023 Zhen, Zou, Wang, Zhou, Dong and Zhang. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neuroscience
Zhen, Fangyuan
Zou, Tongdan
Wang, Ting
Zhou, Yongwei
Dong, Shuqian
Zhang, Houbin
Rhodopsin-associated retinal dystrophy: Disease mechanisms and therapeutic strategies
title Rhodopsin-associated retinal dystrophy: Disease mechanisms and therapeutic strategies
title_full Rhodopsin-associated retinal dystrophy: Disease mechanisms and therapeutic strategies
title_fullStr Rhodopsin-associated retinal dystrophy: Disease mechanisms and therapeutic strategies
title_full_unstemmed Rhodopsin-associated retinal dystrophy: Disease mechanisms and therapeutic strategies
title_short Rhodopsin-associated retinal dystrophy: Disease mechanisms and therapeutic strategies
title_sort rhodopsin-associated retinal dystrophy: disease mechanisms and therapeutic strategies
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10106759/
https://www.ncbi.nlm.nih.gov/pubmed/37077319
http://dx.doi.org/10.3389/fnins.2023.1132179
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