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Arup Das, MD, PhD; Angela McLamore, MS; Wanmin Song; Paul G. McGuire, PhD

Arch Ophthalmol. 1999;117:498-503.

Objectives  To determine the role of extracellular proteinases in ischemia-induced retinal neovascularization in an animal model and to examine the effect of proteinase inhibitors on retinal neovascularization.

Methods  Retinal neovascularization was induced in newborn mice exposed to 75% oxygen for 5 days, followed by room air. Retinal extracts underwent zymographic analysis to measure the activity of urokinase and matrix metalloproteinases (MMPs). Some animals under the same conditions also received intraperitoneal injections of an MMP inhibitor. Histological analysis was done to quantitate the neovascular response in these animals.

Results  Levels of urokinase and MMPs (MMP-2 and MMP-9) in retinas were significantly increased in animals with induced retinal neovascularization. Neovascularization was significantly inhibited with intraperitoneal administration of an MMP inhibitor.

Conclusion  Systemic inhibition of MMPs may have therapeutic potential in preventing retinopathy associated with retinal neovascularization.

Clinical Relevance  Because up-regulation and activation of proteinases represents a final common pathway in the process of retinal neovascularization, pharmacological intervention of this pathway may be an alternative therapeutic approach to proliferative retinopathy.

From the Division of Ophthalmology (Dr Das and Ms McLamore) and the Department of Cell Biology and Physiology (Ms Song and Dr McGuire), University of New Mexico School of Medicine, and the Division of Ophthalmology, Veterans Affairs Administration Medical Center (Dr Das), Albuquerque.

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