Loss of αA or αB-Crystallin Accelerates Photoreceptor Cell Death in a Mouse Model of P23H Autosomal Dominant Retinitis Pigmentosa |
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| Authors: | Tiantian Wang Jingyu Yao Lin Jia Patrice E. Fort David N. Zacks |
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| Affiliation: | 1.Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, MI 48105, USA; (T.W.); (J.Y.); (L.J.); (P.E.F.);2.Department of Ophthalmology, Xiangya Hospital, Xiangya School of Medicine, Central South University, Changsha 410008, China |
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| Abstract: | Inherited retinal degenerations (IRD) are a leading cause of visual impairment and can result from mutations in any one of a multitude of genes. Mutations in the light-sensing protein rhodopsin (RHO) is a leading cause of IRD with the most common of those being a missense mutation that results in substitution of proline-23 with histidine. This variant, also known as P23H-RHO, results in rhodopsin misfolding, initiation of endoplasmic reticulum stress, the unfolded protein response, and activation of cell death pathways. In this study, we investigate the effect of α-crystallins on photoreceptor survival in a mouse model of IRD secondary to P23H-RHO. We find that knockout of either αA- or αB-crystallin results in increased intraretinal inflammation, activation of apoptosis and necroptosis, and photoreceptor death. Our data suggest an important role for the ⍺-crystallins in regulating photoreceptor survival in the P23H-RHO mouse model of IRD. |
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| Keywords: | α -crystallin, P23H, autophagy, cell death, microglia |
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