Lysosomes: Regulators of autophagy in the retinal pigmented epithelium

Debasish Sinha, Mallika Valapala, Peng Shang, Stacey Hose, Rhonda Grebe, Gerard A. Lutty, J. Samuel Zigler, Kai Kaarniranta, James T. Handa

Research output: Contribution to journalReview articlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)46-53
Number of pages8
JournalExperimental eye research
Volume144
DOIs
StatePublished - Mar 1 2016

Keywords

  • AMD
  • Autophagy
  • Lysosome
  • MTORC1
  • Oxidative stress
  • RPE
  • V-ATPase
  • βA3/A1-crystallin

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

Fingerprint

Dive into the research topics of 'Lysosomes: Regulators of autophagy in the retinal pigmented epithelium'. Together they form a unique fingerprint.

Cite this