Abstract
To develop an in vivo model of chronic optic nerve ischemia to study the role of vascular insufficiency in the development of glaucomatous optic neuropathy. We surgically implanted osmotically-driven mini-pumps that allowed the continuous micro-application of 0.2 micrograms/day of endothelin-1 (ET-1) into the retrobulbar optic nerve of rabbits and rhesus monkeys. ET-1 was delivered for 2 to 6 months, following which histological studies were performed. Both rabbits and primates experienced a 35% to 38% decrease in optic nerve blood flow with corresponding focal narrowing of the vessels supplying the optic nerve. In the rabbit model, optic disc excavation and histologic tissue loss in the anterior optic nerve resulted from the induced ischemia. Chronic ischemia of the primate anterior optic nerve induced with endothelin-1 infusion resulted in diffuse loss of axons without a change in the intraocular pressure.
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