Sensitivity of ocular anterior chamber tissues to oxidative damage and its relevance to the pathogenesis of glaucoma.
OBJECTIVE
The anterior chamber of the eye is a highly specialized structure delimited by the cornea, lens, and iris. It contains the aqueous humor, secreted by the ciliary body and drained by the trabecular meshwork. Alteration of aqueous humor homeostasis plays a major role in the pathogenesis of glaucoma. The trabecular meshwork is the target tissue of glaucoma in the anterior chamber, and the development and progression of glaucoma are accompanied by accumulation of oxidative damage in this tissue. This study was conducted to comparatively evaluate the sensitivity to oxidative stress of anterior chamber tissues including the cornea, iris, and trabecular meshwork.


METHODS
Cornea, iris, and trabecular meshwork fragments collected from six cornea donors were either left untreated or treated with hydrogen peroxide. Oxidative damage was determined by evaluating nucleotide oxidative modifications (8-hydroxy-2'-deoxyguanosine) and apurinic alkali-fragile sites by capillary electrophoresis.


RESULTS
The results indicated that the basal level of oxidative nucleotide modifications was higher in the cornea than in the iris and trabecular meshwork. The trabecular meshwork was the most sensitive tissue to oxidative damage, as after exposure to hydrogen peroxide both markers of oxidative damage dramatically increased in the trabecular meshwork but not in the cornea and iris.


CONCLUSIONS
Because the cornea and iris are directly exposed to light, they possess antioxidant defense mechanisms that are not activated in the trabecular meshwork. The peculiar sensitivity of the trabecular meshwork to oxidative stress is consistent with the damage selectively induced in it, triggering glaucoma's pathogenic cascade.
Izzotti
Alberto
A
Department of Health Sciences, Faculty of Medicine, University of Genoa, Genoa, Italy. izzotti@unige.it
Saccà
Sergio C
SC
Longobardi
Mariagrazia
M
Cartiglia
Cristina
C
D000080242:8-Hydroxy-2'-Deoxyguanosine; D003315:Cornea / Q000187:drug effects* / Q000378:metabolism; D004249:DNA Damage; D053938:DNA Fragmentation; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D019075:Electrophoresis, Capillary; D005901:Glaucoma / Q000209:etiology*; D005982:Glutathione Transferase / Q000235:genetics; D006801:Humans; D006861:Hydrogen Peroxide / Q000633:toxicity*; D007498:Iris / Q000187:drug effects* / Q000378:metabolism; D018384:Oxidative Stress; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D014129:Trabecular Meshwork / Q000187:drug effects* / Q000378:metabolism
D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine; D005982:Glutathione Transferase; D006861:Hydrogen Peroxide