通过涉及 Müller 胶质细胞中 RGR 视蛋白的机制实现视锥视觉色素的光驱动再生。
Light-Driven Regeneration of Cone Visual Pigments through a Mechanism Involving RGR Opsin in Müller Glial Cells.
机构信息
Stein Eye Institute and Department of Ophthalmology, University of California, Los Angeles, Los Angeles, CA, USA.
Stein Eye Institute and Department of Ophthalmology, University of California, Los Angeles, Los Angeles, CA, USA; Department of Integrative Biology and Physiology, University of California, Los Angeles, Los Angeles, CA, USA.
出版信息
Neuron. 2019 Jun 19;102(6):1172-1183.e5. doi: 10.1016/j.neuron.2019.04.004. Epub 2019 May 2.
While rods in the mammalian retina regenerate rhodopsin through a well-characterized pathway in cells of the retinal pigment epithelium (RPE), cone visual pigments are thought to regenerate in part through an additional pathway in Müller cells of the neural retina. The proteins comprising this intrinsic retinal visual cycle are unknown. Here, we show that RGR opsin and retinol dehydrogenase-10 (Rdh10) convert all-trans-retinol to 11-cis-retinol during exposure to visible light. Isolated retinas from Rgr+/+ and Rgr-/- mice were exposed to continuous light, and cone photoresponses were recorded. Cones in Rgr-/- retinas lost sensitivity at a faster rate than cones in Rgr+/+ retinas. A similar effect was seen in Rgr+/+ retinas following treatment with the glial cell toxin, α-aminoadipic acid. These results show that RGR opsin is a critical component of the Müller cell visual cycle and that regeneration of cone visual pigment can be driven by light.
虽然哺乳动物视网膜中的视杆细胞通过视网膜色素上皮（RPE）细胞中的一条特征明确的途径再生视紫红质，但视锥视觉色素被认为部分通过神经视网膜中的 Müller 细胞中的另一条途径再生。构成这种内在视网膜视觉循环的蛋白质尚不清楚。在这里，我们表明 RGR 视蛋白和视黄醇脱氢酶-10（Rdh10）在暴露于可见光时将全反式视黄醇转化为 11-顺式视黄醇。将 Rgr+/+ 和 Rgr-/- 小鼠的分离视网膜暴露于连续光下，并记录视锥光反应。与 Rgr+/+ 视网膜中的视锥相比，Rgr-/- 视网膜中的视锥丧失敏感性的速度更快。在用神经胶质细胞毒素 α-氨基己二酸处理后，在 Rgr+/+ 视网膜中也观察到类似的效果。这些结果表明 RGR 视蛋白是 Müller 细胞视觉循环的关键组成部分，并且视锥视觉色素的再生可以由光驱动。
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