Retinoic acid signaling mediates peripheral cone photoreceptor survival in a mouse model of retina degeneration.
Retinoic acid signaling mediates peripheral cone photoreceptor survival in a mouse model of retina degeneration.
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DOI：
10.7554/elife.76389
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发表时间：
2022-03-22
期刊：
影响因子：
7.7
通讯作者：
Cepko CL
中科院分区：
文献类型：
--
作者：
Amamoto R;Wallick GK;Cepko CL
色素性视网膜炎（RP）是一种进行性的，使人衰弱的视觉障碍，由一组不同的基因突变引起。在患有RP的人类和RP的小鼠模型中，视杆细胞感光器功能障碍导致夜视能力丧失，随后是继发性视锥细胞感光器功能障碍和变性，导致日光色觉丧失。预防继发性视锥细胞死亡的策略可以提供一种通用的RP治疗，以保护日光色觉，而不管潜在的突变。在RP的小鼠模型中，周边视网膜中的视锥细胞长期存活，尽管视杆细胞完全丧失。这种外周视锥细胞存活的机制还没有被探索。在这里，我们发现，活跃的视黄酸（RA）信号在外周米勒神经胶质细胞是必要的异常长的生存这些周边锥。RA消耗条件性敲除RA合成酶，或过度表达的RA降解酶，废除了外周锥细胞的生存期延长。相反，RA信号在视网膜中央的组成性激活促进长期锥生存。这些结果表明，RA信号介导的rd1视网膜变性小鼠模型中的延长的外周视锥细胞存活，并提供了一个通用的策略，在许多疾病，导致视锥细胞介导的视力丧失的视锥细胞存活的基础。
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.
影响因子：
4.4
作者：
Patel TP;Vongsachang H;Schilling A;Kong X;Singh MS
通讯作者：
Singh MS