Retinal neovascularization is suppressed with a matrix metalloproteinase inhibitor

Objectives: To determine the role of extracellular proteinases in ischemia- induced retinal neovascularization in an animal model and to examine the ef fect 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 zym ographic analysis to measure the activity of urokinase and matrix metallopr oteinases (MMPs). Some animals under the same conditions also received intr aperitoneal 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 sig nificantly increased in animals with induced retinal neovascularization. Ne ovascularization was significantly inhibited with intraperitoneal administr ation of an MMP inhibitor. Conclusion: Systemic inhibition of MMPs may have therapeutic potential in p reventing retinopathy associated with retinal neovascularization. Clinical Relevance: Because up-regulation and activation of proteinases rep resents a final common pathway in the process of retinal neovascularization , pharmacological intervention of this pathway may be an alternative therap eutic approach to proliferative retinopathy.