Hypoxia-ischemia and retinal ganglion cell damage
Authors: Charanjit Kaur, Wallace S Foulds, Eng-Ang Ling
Published Date August 2008
Volume 2008:2(4) Pages 879 - 889
DOI: http://dx.doi.org/10.2147/OPTH.S3361
Charanjit Kaur1, Wallace S Foulds2, Eng-Ang Ling1
1Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; 2Singapore Eye Research Institute, Singapore
Abstract:
Retinal hypoxia is the potentially blinding mechanism underlying a
number of sight-threatening disorders including central retinal artery
occlusion, ischemic central retinal vein thrombosis, complications of
diabetic eye disease and some types of glaucoma. Hypoxia is implicated
in loss of retinal ganglion cells (RGCs) occurring in such conditions.
RGC death occurs by apoptosis or necrosis. Hypoxia-ischemia induces the
expression of hypoxia inducible factor-1α and its target genes such as
vascular endothelial growth factor (VEGF) and nitric oxide synthase
(NOS). Increased production of VEGF results in disruption of the blood
retinal barrier leading to retinal edema. Enhanced expression of NOS
results in increased production of nitric oxide which may be toxic to
the cells resulting in their death. Excess glutamate release in
hypoxic-ischemic conditions causes excitotoxic damage to the RGCs
through activation of ionotropic and metabotropic glutamate receptors.
Activation of glutamate receptors is thought to initiate damage in the
retina by a cascade of biochemical effects such as neuronal NOS
activation and increase in intracellular Ca2+ which has been
described as a major contributing factor to RGC loss. Excess production
of proinflammatory cytokines also mediates cell damage. Besides the
above, free-radicals generated in hypoxic-ischemic conditions result in
RGC loss because of an imbalance between antioxidant- and
oxidant-generating systems. Although many advances have been made in
understanding the mediators and mechanisms of injury, strategies to
improve the damage are lacking. Measures to prevent neuronal injury have
to be developed.
Source: http://www.dovepress.com/hypoxia-ischemia-and-retinal-ganglion-cell-damage-peer-reviewed-article-OPTH-recommendation1
Source: http://www.dovepress.com/hypoxia-ischemia-and-retinal-ganglion-cell-damage-peer-reviewed-article-OPTH-recommendation1
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