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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...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2022
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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. |
format | Online Article Text |
id | pubmed-8940176 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
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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