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Abstract

Purpose To evaluate the neuroprotective and/or oculohypotensive effects of potent angiotensin system agents known to reduce intraocular pressure in the normotensive rabbits by using an experimental laser-induced glaucoma model in rat eye.

Methods Experimental glaucoma was induced unilaterally using laser photocoagulation of the episcleral and limbal veins of male Wistar rats twice in one week intervals. The fellow eye was untreated, thus serving as a normotensive control. Mas receptor agonist angiotensin (1-7) and antagonist A-779 as well as their combination were injected intravitreally. IOP was measured by rebound tonometer during the follow-up time of two weeks. At the end of the study the animals were sacrified. The eyes and the optic nerves were collected. The neurodegenerative changes were evaluated from the optic nerves using a modified Gallyas silver-staining method.

Results Mean IOP in laser treated and untreated eyes were 27.4 mmHg and 10.5 mmHg during two weeks follow up time. A significant axonal destruction was detected in glaucomatous eyes vs fellow eye with normal IOP. Intravitreal administration of test compounds did not reduce IOP. However the group of rats that were treated with A-779 had significantly lower area of neurodegenerative axons in the optic nerves as compared to the other groups.

Conclusion In laser induced glaucoma model IOP elevates rapidly leading to severe destruction of ganglion cell axons like occurs in normally slowly developing neuropathy. In this model Mas receptor antagonist A-779 had an IOP-independent neuroprotective effect on retinal ganglion cells whereas Mas receptor stimulation did not reduce IOP and had no influence on axonal damage.