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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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2022-03-01
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| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/76389 |
| _version_ | 1811236067490136064 |
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| author | Ryoji Amamoto Grace K Wallick Constance L Cepko |
| author_facet | Ryoji Amamoto Grace K Wallick Constance L Cepko |
| author_sort | Ryoji Amamoto |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-04-12T12:02:36Z |
| format | Article |
| id | doaj.art-7260d51236774fecbd6b2410649f4948 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T12:02:36Z |
| publishDate | 2022-03-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-7260d51236774fecbd6b2410649f49482022-12-22T03:33:48ZengeLife Sciences Publications LtdeLife2050-084X2022-03-011110.7554/eLife.76389Retinoic acid signaling mediates peripheral cone photoreceptor survival in a mouse model of retina degenerationRyoji Amamoto0https://orcid.org/0000-0002-9335-112XGrace K Wallick1Constance L Cepko2https://orcid.org/0000-0002-9945-6387Department of Genetics and Ophthalmology, Howard Hughes Medical Institute, Blavatnik Institute, Harvard Medical School, Boston, United StatesDepartment of Genetics and Ophthalmology, Howard Hughes Medical Institute, Blavatnik Institute, Harvard Medical School, Boston, United StatesDepartment of Genetics and Ophthalmology, Howard Hughes Medical Institute, Blavatnik Institute, Harvard Medical School, Boston, United StatesRetinitis 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.https://elifesciences.org/articles/76389retinadegenerationconesphotoreceptorretinitis pigmentosa |
| spellingShingle | Ryoji Amamoto Grace K Wallick Constance L Cepko Retinoic acid signaling mediates peripheral cone photoreceptor survival in a mouse model of retina degeneration eLife retina degeneration cones photoreceptor retinitis pigmentosa |
| 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 | retina degeneration cones photoreceptor retinitis pigmentosa |
| url | https://elifesciences.org/articles/76389 |
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