Glaucomatous outflow pathway and oxidative stress.
Oxidative free radicals and reactive oxygen species (ROS) are able to affect the cellularity of the human trabecular meshwork (HTM). These findings suggest that intraocular pressure increase, which characterises most glaucomas, is related to oxidative degenerative processes affecting the HTM and specifically its endothelial cells. Much evidence indicates that in this region ROS play a fundamental pathogenic role by reducing local antioxidant activities, inducing outflow resistance and exacerbating the activities of superoxide dismutase and glutathione peroxidase in glaucomatous eyes. Furthermore, hydrogen peroxide induces rearrangement of HTM cells and compromises their integrity. Glaucomatous subjects might have a genetic predisposition rendering them more susceptible to ROS-induced damage. A fairly significant correlation between oxidative DNA damage in the HTM and intraocular pressure increase and visual field defects in glaucomatous patients has been demonstrated. Thus, oxidative stress may play a significant role during glaucoma course initially damaging HTM cells, then contributing to the alteration of the homeostasis between NO and endothelins, and finally through its possible involvement in ganglional cell death. On the whole, these findings support the hypothesis that oxidative damage is an important step in the pathogenesis of primary open-angle glaucoma, and might be a relevant target for both prevention and therapy.
Saccà
Sergio Claudio
SC
San Martino Hospital, Section of Ophthalmology, Largo Rosanna Benzi 1, 16132 Genova, Italy. sergio.sacca@hsanmartino.it
Izzotti
Alberto
A
Rossi
Pietro
P
Traverso
Carlo
C
D004249:DNA Damage; D016232:Endothelins / Q000378:metabolism; D020022:Genetic Predisposition to Disease; D005902:Glaucoma, Open-Angle / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D009569:Nitric Oxide / Q000378:metabolism; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism; D014129:Trabecular Meshwork / Q000378:metabolism / Q000473:pathology
D016232:Endothelins; D017382:Reactive Oxygen Species; D009569:Nitric Oxide