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Abstract #20092 Published in IGR 9-4
Oxidative stress is an early event in hydrostatic pressure induced retinal ganglion cell damage
Liu Q; Ju WK; Crowston JG; Xie F; Perry G; Smith MA; Lindsey JD; Weinreb RNInvestigative Ophthalmology and Visual Science 2007; 48: 4580-4589
See also comment(s) by Keith Martin •
PURPOSE: To determine whether oxidative adduct formation or heme oxygenase-1 (HO-1) expression are altered in retinal ganglion cell (RGC) cultures exposed to elevated hydrostatic pressure and in a mouse model of glaucoma. METHODS: Cultured RGC-5 cells were subjected to 0, 30, 60, or 100 mmHg hydrostatic pressure for two hours, and the cells were harvested. Parallel experiments examined the recovery from this stress, the effect of direct 4-hydroxy-2-nonenal (HNE) treatment, and the effect of pretreatment with resveratrol or quercetin. Mice were anesthetized and intraocular pressure was increased to 30, 60, or 100 mmHg for one hour; then the retinas were harvested. HNE adduct formation and HO-1 expression were assessed by immunocytochemistry and immunoblotting. RESULTS: Increases of HNE-protein adducts (up to 5-fold) and HO-1 expression (up to 2.5 fold) in pressure-treated RGC-5 cells were dose dependent. During recovery experiments, HNE-protein adducts continued to increase for up to ten hours; in contrast, HO-1 expression decreased immediately. HNE, at a concentration as low as 5μM, led to neurotoxicity in RGC-5 cells. HNE adducts and HO-1 expression increased in the mouse retina and optic nerve after acute IOP elevation up to 5.5-fold and 2-fold, respectively. Antioxidant treatment reduced the oxidative stress level in pressure-treated RGC-5 cells. CONCLUSIONS: This study demonstrates that oxidative stress is an early event in hydrostatic pressure/IOP-induced neuronal damage. These findings support the view that oxidative damage contributes early to glaucomatous optic neuropathy.
Dr. Q. Li, Hamilton Glaucoma Center and the Department of Ophthalmology, University of California San Diego, La Jolla, California 92037-0946, USA
Classification:
5.1 Rodent (Part of: 5 Experimental glaucoma; animal models)
2.13 Retina and retinal nerve fibre layer (Part of: 2 Anatomical structures in glaucoma)
11.8 Neuroprotection (Part of: 11 Medical treatment)