Department of Ophthalmology and Visual Sciences, Washington University, St. Louis School of Medicine, St. Louis, MO 63110, USA.
Cell. 2013 Jul 18;154(2):365-76. doi: 10.1016/j.cell.2013.06.012.
Phagocytosis and degradation of photoreceptor outer segments (POS) by retinal pigment epithelium (RPE) is fundamental to vision. Autophagy is also responsible for bulk degradation of cellular components, but its role in POS degradation is not well understood. We report that the morning burst of RPE phagocytosis coincided with the enzymatic conversion of autophagy protein LC3 to its lipidated form. LC3 associated with single-membrane phagosomes containing engulfed POS in an Atg5-dependent manner that required Beclin1, but not the autophagy preinitiation complex. The importance of this process was verified in mice with Atg5-deficient RPE cells that showed evidence of disrupted lysosomal processing. These mice also exhibited decreased photoreceptor responses to light stimuli and decreased chromophore levels that were restored with exogenous retinoid supplementation. These results establish that the interplay of phagocytosis and autophagy within the RPE is required for both POS degradation and the maintenance of retinoid levels to support vision.
光感受器外节（POS）被视网膜色素上皮（RPE）吞噬和降解是视觉的基础。自噬也负责细胞成分的大量降解，但它在 POS 降解中的作用尚不清楚。我们报告说，RPE 吞噬的清晨爆发与自噬蛋白 LC3 酶转化为其脂质化形式同时发生。LC3 与含有被吞噬 POS 的单膜吞噬体相关，这种关联依赖于 Atg5，但不依赖于自噬起始复合物。该过程的重要性在 Atg5 缺陷型 RPE 细胞的小鼠中得到了验证，这些细胞显示出溶酶体处理中断的证据。这些小鼠还表现出对光刺激的光感受器反应下降和视黄醛水平下降，而外源性视黄醇补充可恢复这些水平。这些结果表明，RPE 内吞噬作用和自噬的相互作用对于 POS 降解和维持视黄醇水平以支持视觉都是必需的。
