Contribution of autophagy to ocular hypertension and neurodegeneration in the DBA/2J spontaneous glaucoma mouse model

Cell Death Discovery
Joshua HirtPaloma B Liton

Abstract

Glaucoma is a progressive optic neuropathy characterized by axonal degeneration and retinal ganglion cells loss. Several factors have been postulated to play a role in glaucoma, elevated intraocular pressure (IOP) being the best well-known causative factor. The mechanisms leading to ocular hypertension and glaucoma are still not fully understood. An increasing number of evidence indicates a role of autophagy in the pathophysiological process of ocular hypertension and glaucoma. However, while all of the studies agree that autophagy is induced in RGCs in response to injury, autophagy was found to either protect or promote cell death depending on the experimental model used. In order to gain more insight into both, the role of autophagy in the pathogenesis of glaucoma and the effect of chronic IOP elevation in the autophagy pathway, we have investigated here for the first time autophagy in the iridocorneal angle region, retinal ganglion cell bodies, and ON axons in the spontaneous ocular hypertensive DBA/2J mouse glaucoma model and in the transgenic DBA/2J::GFP-LC3 mice, generated in our laboratory. Our results indicate decreased autophagic flux in the outflow pathway cells in the DBA/2J mice, characterized by increased levels of...Continue Reading

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Citations

Jul 11, 2019·Current Molecular Medicine·Jing WangHua Yan
Sep 18, 2020·Investigative Ophthalmology & Visual Science·Michael L De IesoMichael H Elliott
Mar 27, 2020·Frontiers in Cell and Developmental Biology·Annagrazia AdornettoRossella Russo
Jul 13, 2019·Frontiers in Cellular Neuroscience·Paula V SubiradaMaría C Sánchez
Dec 16, 2020·Investigative Ophthalmology & Visual Science·Oliver W GramlichMarkus H Kuehn
Feb 15, 2021·Survey of Ophthalmology·Luciano QuarantaIvano Riva
Mar 7, 2021·Life·José A Fernández-AlbarralAna I Ramírez
Mar 24, 2021·Proceedings of the National Academy of Sciences of the United States of America·Myoung Sup ShimPaloma B Liton
Aug 20, 2021·Investigative Ophthalmology & Visual Science·Max K ColbertKevin C Chan
Aug 31, 2021·The EMBO Journal·Daniel J KlionskyFederico Pietrocola

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Methods Mentioned

BETA
transgenic
genotyping
PCR
electron microscopy
protein assay

Software Mentioned

Image J
MATLAB
GraphPad Prism

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