title: Lysosomes: Regulators of autophagy in the retinal pigmented epithelium.
abstract: 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 βA3/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 βA3/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 βA3/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.
authors: Wilmer Eye Institute, The Johns Hopkins University School of Medicine, Baltimore, MD, USA. Electronic address: Debasish@jhmi.edu.
authors: Debasish
authors: D
authors: Sinha
authors: Wilmer Eye Institute, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors: Mallika
authors: M
authors: Valapala
authors: Wilmer Eye Institute, The Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Ophthalmology of Shanghai Tenth Hospital and Tongji Eye Institute, Tongji University School of Medicine, Shanghai, China.
authors: Peng
authors: P
authors: Shang
authors: Wilmer Eye Institute, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors: Stacey
authors: S
authors: Hose
authors: Wilmer Eye Institute, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors: Rhonda
authors: R
authors: Grebe
authors: Wilmer Eye Institute, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors: Gerard A
authors: GA
authors: Lutty
authors: Wilmer Eye Institute, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors: J Samuel
authors: JS
authors: Zigler
authors: Department of Ophthalmology, Institute of Clinical Medicine and Kuopio University Hospital, University of Eastern Finland, Kuopio, Finland.
authors: Kai
authors: K
authors: Kaarniranta
authors: Wilmer Eye Institute, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors: James T
authors: JT
authors: Handa
mesh_terms: D000818:Animals; D001343:Autophagy / Q000502:physiology*; D006801:Humans; D008247:Lysosomes / Q000502:physiology*; D000076222:Mechanistic Target of Rapamycin Complex 1; D046912:Multiprotein Complexes / Q000502:physiology; D001678:Organelle Biogenesis; D055213:Retinal Pigment Epithelium / Q000378:metabolism*; D058570:TOR Serine-Threonine Kinases / Q000502:physiology
chemical_list: D046912:Multiprotein Complexes; D000076222:Mechanistic Target of Rapamycin Complex 1; D058570:TOR Serine-Threonine Kinases
keywords: AMD; Autophagy; Lysosome; Oxidative stress; RPE; V-ATPase; mTORC1; βA3/A1-crystallin