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Ocular hypertension is a symptom of a glaucomatous condition characterized by a severe vision decrease. Blindness caused by the apoptotic death of the retinal ganglion cells and of the astrocytes of the optic nerve may eventually result. Experimental hypertension was induced by inoculation of methylcellulose in the anterior chamber. Chromatin staining, TUNEL assay, and inter-nucleosomal DNA fragmentation observed in retina and optic nerve strongly suggest that hypertension causes apoptosis. Immunolocalization of the fibrillary acidic glial protein, specific of cell stress, and caspase-3 in the same tissues, further support this mode of cell death. Activation of the ubiquitin dependent proteolytic system was also observed. Protection from apoptosis exerted by administration of the peroxide scavenger trolox, suggests that the apoptotic pathway is activated by an oxidative stress. The data presented here show that the experimental hypertensive insult induces degenerative and apoptotic events comparable to those observed in human glaucoma.