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Scripps Team Shows Potential of microRNA Knockdown for Ocular Diseases

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Investigators from the Scripps Research Institute have published new preclinical data indicating that inhibiting microRNA-132 in the eye can prevent the neovascularization associated with wet age-related macular degeneration and similar eye conditions.

In the study, which appears in the Journal of Clinical Investigation, Scripps scientists led by Martin Friedlander found that the Ras pathway, which functions downstream of a number of cytokines including the angiogenic protein vascular endothelial growth factor, is "active in the growing vascular front of developing and pathological vascular networks."

They also observed that the endogenous Ras inhibitor p120RasGAP is downregulated in mouse models of pathological ocular angiogenesis.

Building off of data published last year by a University of California, San Diego group that show miR-132 acts as an "angiogenic switch" by targeting p120RasGAP in the endothelium and inducing neovascularization, the Scripps researchers demonstrated that blocking expression of the miRNA boosted p120RasGAP levels. In doing so, the anti-miRNA treatment promoted quiescence and prevented neovascularization, they wrote in JCI.

“We believe that targeting and inhibiting the action of microRNAs involved could represent a novel and effective way to treat a broad range of neovascular eye diseases such as diabetic retinopathy, macular degeneration, and macular telangiectasia," Friedlander said in a statement.

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