TY - JOUR TI - Retinoic acid signaling mediates peripheral cone photoreceptor survival in a mouse model of retina degeneration AU - Amamoto, Ryoji AU - Wallick, Grace K AU - Cepko, Constance L A2 - Bovolenta, Paola A2 - Moore, Tirin A2 - Leinonen, Henri VL - 11 PY - 2022 DA - 2022/03/22 SP - e76389 C1 - eLife 2022;11:e76389 DO - 10.7554/eLife.76389 UR - https://doi.org/10.7554/eLife.76389 AB - 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. KW - retina KW - degeneration KW - cones KW - photoreceptor KW - retinitis pigmentosa JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -