Lysosomes: Regulators of autophagy in the retinal pigmented epithelium

被引:71
作者
Sinha, Debasish [1 ]
Valapala, Mallika [1 ]
Shang, Peng [1 ,2 ,3 ]
Hose, Stacey [1 ]
Grebe, Rhonda [1 ]
Lutty, Gerard A. [1 ]
Zigler, J. Samuel, Jr. [1 ]
Kaarniranta, Kai [4 ,5 ]
Handa, James T. [1 ]
机构
[1] Johns Hopkins Univ, Wilmer Eye Inst, Sch Med, Baltimore, MD 21287 USA
[2] Tongji Univ, Sch Med, Dept Ophthalmol, Shanghai Hosp 10, Shanghai 200092, Peoples R China
[3] Tongji Univ, Sch Med, Tongji Eye Inst, Shanghai 200092, Peoples R China
[4] Univ Eastern Finland, Dept Ophthalmol, Inst Clin Med, Kuopio, Finland
[5] Univ Eastern Finland, Kuopio Univ Hosp, Kuopio, Finland
基金
美国国家卫生研究院;
关键词
AMD; Autophagy; beta A3/A1-crystallin; Lysosome; mTORC1; Oxidative stress; RPE; V-ATPase; FACTOR-H POLYMORPHISM; OXIDATIVE STRESS; NLRP3; INFLAMMASOME; MACULAR DEGENERATION; NALP3; AMINO-ACIDS; RPE CELLS; MTOR; DEGRADATION; ACTIVATION;
D O I
10.1016/j.exer.2015.08.018
中图分类号
R77 [眼科学];
学科分类号
100212 ;
摘要
The retinal pigmented epithelium (RPE) is critically important to retinal homeostasis, in part due to its very active processes of phagocytosis and autophagy. Both of these processes depend upon the normal functioning of lysosomes, organelles which must fuse with (auto)phagosomes to deliver the hydrolases that effect degradation of cargo. It has become clear that signaling through mTOR complex 1 (mTORC1), is very important in the regulation of lysosomal function. This signaling pathway is becoming a target for therapeutic intervention in diseases, including age-related macular degeneration (AMD), where lysosomal function is defective. In addition, our laboratory has been studying animal models in which the gene (Cryba1) for beta A3/A1-crystallin is deficient. These animals exhibit impaired lysosomal clearance in the RPE and pathological signs that are similar to some of those seen in AMD patients. The data demonstrate that beta A3/A1-crystallin localizes to lysosomes in the RPE and that it is a binding partner of V-ATPase, the proton pump that acidifies the lysosomal lumen. This suggests that beta A3/A1-crystallin may also be a potential target for therapeutic intervention in AMD. In this review, we focus on effector molecules that impact the lysosomal autophagic pathway in RPE cells. (C) 2015 Elsevier Ltd. All rights reserved.
引用
收藏
页码:46 / 53
页数:8
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