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Retinoic acid signaling mediates peripheral cone photoreceptor survival in a mouse model of retina degeneration

Retinitis Pigmentosa (RP) is a progressive, debilitating visual disorder caused by mutations in a diverse set of genes. In both humans with RP and mouse models of RP, rod photoreceptor dysfunction leads to loss of night vision, and is followed by secondary cone photoreceptor dysfunction and degenera...

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Detalles Bibliográficos
Autores principales: Amamoto, Ryoji, Wallick, Grace K, Cepko, Constance L
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8940176/
https://www.ncbi.nlm.nih.gov/pubmed/35315776
http://dx.doi.org/10.7554/eLife.76389
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author Amamoto, Ryoji
Wallick, Grace K
Cepko, Constance L
author_facet Amamoto, Ryoji
Wallick, Grace K
Cepko, Constance L
author_sort Amamoto, Ryoji
collection PubMed
description Retinitis Pigmentosa (RP) is a progressive, debilitating visual disorder caused by mutations in a diverse set of genes. In both humans with RP and mouse models of RP, rod photoreceptor dysfunction leads to loss of night vision, and is followed by secondary cone photoreceptor dysfunction and degeneration, leading to loss of daylight color vision. A strategy to prevent secondary cone death could provide a general RP therapy to preserve daylight color vision regardless of the underlying mutation. In mouse models of RP, cones in the peripheral retina survive long-term, despite complete rod loss. The mechanism for such peripheral cone survival had not been explored. Here, we found that active retinoic acid (RA) signaling in peripheral Muller glia is necessary for the abnormally long survival of these peripheral cones. RA depletion by conditional knockout of RA synthesis enzymes, or overexpression of an RA degradation enzyme, abrogated the extended survival of peripheral cones. Conversely, constitutive activation of RA signaling in the central retina promoted long-term cone survival. These results indicate that RA signaling mediates the prolonged peripheral cone survival in the rd1 mouse model of retinal degeneration, and provide a basis for a generic strategy for cone survival in the many diseases that lead to loss of cone-mediated vision.
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spelling pubmed-89401762022-03-23 Retinoic acid signaling mediates peripheral cone photoreceptor survival in a mouse model of retina degeneration Amamoto, Ryoji Wallick, Grace K Cepko, Constance L eLife Developmental Biology Retinitis Pigmentosa (RP) is a progressive, debilitating visual disorder caused by mutations in a diverse set of genes. In both humans with RP and mouse models of RP, rod photoreceptor dysfunction leads to loss of night vision, and is followed by secondary cone photoreceptor dysfunction and degeneration, leading to loss of daylight color vision. A strategy to prevent secondary cone death could provide a general RP therapy to preserve daylight color vision regardless of the underlying mutation. In mouse models of RP, cones in the peripheral retina survive long-term, despite complete rod loss. The mechanism for such peripheral cone survival had not been explored. Here, we found that active retinoic acid (RA) signaling in peripheral Muller glia is necessary for the abnormally long survival of these peripheral cones. RA depletion by conditional knockout of RA synthesis enzymes, or overexpression of an RA degradation enzyme, abrogated the extended survival of peripheral cones. Conversely, constitutive activation of RA signaling in the central retina promoted long-term cone survival. These results indicate that RA signaling mediates the prolonged peripheral cone survival in the rd1 mouse model of retinal degeneration, and provide a basis for a generic strategy for cone survival in the many diseases that lead to loss of cone-mediated vision. eLife Sciences Publications, Ltd 2022-03-22 /pmc/articles/PMC8940176/ /pubmed/35315776 http://dx.doi.org/10.7554/eLife.76389 Text en © 2022, Amamoto et al https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Developmental Biology
Amamoto, Ryoji
Wallick, Grace K
Cepko, Constance L
Retinoic acid signaling mediates peripheral cone photoreceptor survival in a mouse model of retina degeneration
title Retinoic acid signaling mediates peripheral cone photoreceptor survival in a mouse model of retina degeneration
title_full Retinoic acid signaling mediates peripheral cone photoreceptor survival in a mouse model of retina degeneration
title_fullStr Retinoic acid signaling mediates peripheral cone photoreceptor survival in a mouse model of retina degeneration
title_full_unstemmed Retinoic acid signaling mediates peripheral cone photoreceptor survival in a mouse model of retina degeneration
title_short Retinoic acid signaling mediates peripheral cone photoreceptor survival in a mouse model of retina degeneration
title_sort retinoic acid signaling mediates peripheral cone photoreceptor survival in a mouse model of retina degeneration
topic Developmental Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8940176/
https://www.ncbi.nlm.nih.gov/pubmed/35315776
http://dx.doi.org/10.7554/eLife.76389
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