The physiological and pathophysiological roles of the autophagy lysosomal system in the conventional aqueous humor outflow pathway: More than cellular clean up.

Journal Article (Journal Article;Review)

During the last few years, the autophagy lysosomal system is emerging as a central cellular pathway with roles in survival, acting as a housekeeper and stress response mechanism. Studies by our and other labs suggest that autophagy might play an essential role in maintaining aqueous humor outflow homeostasis, and that malfunction of autophagy in outflow pathway cells might predispose to ocular hypertension and glaucoma pathogenesis. In this review, we will collect the current knowledge and discuss the molecular mechanisms by which autophagy does or might regulate normal outflow pathway tissue function, and its response to different types of stressors (oxidative stress and mechanical stress). We will also discuss novel roles of autophagy and lysosomal enzymes in modulation of TGFβ signaling and ECM remodeling, and the link between dysregulated autophagy and cellular senescence. We will examine what we have learnt, using pre-clinical animal models about how dysregulated autophagy can contribute to disease and apply that to the current status of autophagy in human glaucoma. Finally, we will consider and discuss the challenges and the potential of autophagy as a therapeutic target for the treatment of ocular hypertension and glaucoma.

Full Text

Duke Authors

Cited Authors

  • Shim, MS; Liton, PB

Published Date

  • September 2022

Published In

Volume / Issue

  • 90 /

Start / End Page

  • 101064 -

PubMed ID

  • 35370083

Pubmed Central ID

  • PMC9464695

Electronic International Standard Serial Number (EISSN)

  • 1873-1635

Digital Object Identifier (DOI)

  • 10.1016/j.preteyeres.2022.101064

Language

  • eng

Conference Location

  • England