Department of Ophthalmology, Peking University People's Hospital & Beijing Key Laboratory of Diagnosis and Therapy of Retinal and Choroid Diseases, Beijing, 100044, China.
Department of Features, Chinese People's Liberation Army 59th Hospital, Kaiyuan, 661600, China.
Sci China Life Sci. 2019 Feb;62(2):244-256. doi: 10.1007/s11427-018-9357-y. Epub 2018 Sep 19.
The aim of this study was to explore the role of autophagy in response to blue light damage in aged mice and in human retinal pigmented epithelium (hRPE) cells. Blue light damage to the retina was induced in 10-month-old (10 mo) C57 mice and hRPE cells. Flash electroretinography was used to assess retinal function. Retinal structure changes were observed by electron microscopy. Western blot was conducted to determine the expression levels of the following proteins: cleaved caspase-3, p38 mitogen-activated protein kinases, protein kinase R-like endoplasmic reticulum kinase (PERK), autophagy marker light chain 3 (LC3), P62, and Beclin-1. On day 1 after light damage to the 10 mo mice, retinal function was changed. The latent periods of a-wave and b-wave were delayed, and amplitude was reduced. The electron microscopy results revealed mitochondria damage in the retinal pigmented epithelium and a disorganized photoreceptor outer segment (OS). PERK, LC3, and Beclin-1 were upregulated, whereas P62 was not. On day 5 after the blue light damage, restoration of electroretinography and OS was observed. PERK, LC3, and Beclin-1 were downregulated, whereas P62 was not. Protein changes in vitro were consistent with in vivo. The present study provided structural and functional evidence that autophagy plays an important role in the response to blue lightinduced retinal damage.
本研究旨在探讨自噬在老年小鼠和人视网膜色素上皮（hRPE）细胞对蓝光损伤反应中的作用。通过对 10 月龄（10 mo）C57 小鼠和 hRPE 细胞进行蓝光损伤，诱导视网膜蓝光损伤。闪光视网膜电图用于评估视网膜功能。通过电子显微镜观察视网膜结构变化。通过 Western blot 测定以下蛋白的表达水平：裂解的半胱天冬酶-3、p38 丝裂原活化蛋白激酶、蛋白激酶 R 样内质网激酶（PERK）、自噬标志物轻链 3（LC3）、P62 和 Beclin-1。在对 10 mo 小鼠进行光损伤后的第 1 天，视网膜功能发生改变。a 波和 b 波的潜伏期延长，振幅降低。电镜结果显示视网膜色素上皮中线粒体损伤和光感受器外节（OS）排列紊乱。PERK、LC3 和 Beclin-1 上调，而 P62 没有上调。在蓝光损伤后第 5 天，观察到视网膜电图和 OS 的恢复。PERK、LC3 和 Beclin-1 下调，而 P62 没有下调。体外的蛋白变化与体内一致。本研究提供了结构和功能证据，表明自噬在蓝光诱导的视网膜损伤反应中起重要作用。
