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Figure 4: Rho/ROCK pathway and its activation in the development of diabetic retinopathy. RhoA is a small GTP-binding protein, and Rho-kinase (ROCK) is its target protein. Glucose, TNF-α, and TGF-β, elevated in diabetic serum or vitreous, activate Rho/ROCK pathway in endothelial cells or hyalocytes. ROCK activation induces endothelial damage mediated through inactivation of endothelial nitric oxide synthase (eNOS), which has endothelial protective potential. Moreover, ROCK causes firm leukocyte adhesion through the increase of ICAM-1 expression and activation of ezrin, radixin, and moesin (ERM) in endothelial cells. ROCK also has important roles such as leukocyte adhesion, endothelial migration, and contraction of proliferative membrane mediated through myosin light chain (MLC) phosphorylation in diabetic retinopathy. These findings suggest that elevated activity of the Rho/ROCK pathway is involved in the pathogenesis of diabetic microvascular damage, proliferative vitreoretinopathy, and retinal neovascularization.