Vertebrate vision relies on the daily phagocytosis and lysosomal degradation of photoreceptor outer segments (POS) within the retinal pigment epithelium (RPE). However, how these events are controlled by light is largely unknown. Here, we show that the light-responsive miR-211 controls lysosomal biogenesis at the beginning of light-dark transitions in the RPE by targeting Ezrin, a cytoskeleton-associated protein essential for the regulation of calcium homeostasis. miR-211-mediated down-regulation of Ezrin leads to Ca2+ influx resulting in the activation of calcineurin, which in turn activates TFEB, the master regulator of lysosomal biogenesis. Light-mediated induction of lysosomal biogenesis and function is impaired in the RPE from miR-211-/- mice that show severely compromised vision. Pharmacological restoration of lysosomal biogenesis through Ezrin inhibition rescued the miR-211-/- phenotype, pointing to a new therapeutic target to counteract retinal degeneration associated with lysosomal dysfunction.

中文翻译：

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光反应性microRNA miR-211靶向Ezrin来调节溶酶体的生物发生和视网膜细胞清除。

脊椎动物的视力依赖于视网膜色素上皮细胞（RPE）内每日吞噬作用和光感受器外段（POS）的溶酶体降解。然而，如何控制这些事件在很大程度上是未知的。在这里，我们显示了光响应性miR-211通过靶向Ezrin（一种对细胞钙稳态的调节至关重要的细胞骨架相关蛋白），在RPE中的明暗过渡开始时控制溶酶体生物发生。miR-211介导的Ezrin下调导致Ca2 +大量涌入，导致钙调神经磷酸酶激活，进而激活TFEB（溶酶体生物发生的主要调节剂）。在miR-211-/-小鼠的RPE中，光介导的溶酶体生物发生和功能的诱导受到损害，显示严重的视力受损。