Diabetic retinopathy (DR) is a well-known serious complication of
diabetes mellitus (DM), and can eventually advance to end-stage
blindness. In the early stage of DR, endothelial cell barrier disorganized primarily and tight junction (TJ)
protein composition transformed subsequently. The
small GTPase RhoA and its downstream effector
Rho-associated coiled-coil containing protein kinase 1 (ROCK1) regulate a mass of cellular processes, including cell adherence, proliferation, permeability and apoptosis. Although RhoA inhibitors have provided substantial clinical benefit as hypertonicity
therapeutics, their use is limited by complex microenvironment as DR. While ample evidence indicates that TJ can be influenced by the RhoA/ROCK1 signaling, the underlying mechanisms remain incompletely understood. Here, we have uncovered a significant signaling network involved in diabetic
retinal microvascular endothelial dysfunction (RMVED). Our results indicated that the activation of RhoA/ROCK1 pathway due to high
glucose played a key role in microvascular endothelial cell dysfunction (MVED) by way of directly inducing TJ
proteins over-expression during DR. We demonstrated that inhibition of RhoA/ROCK1 may attenuate the hypertonicity of endothelial cell caused by high
glucose microenvironment meanwhile. Besides, chemical and pharmacological inhibitors of RhoA/ROCK1 pathway may partly block
inflammation due to DR. Simultaneously, the apoptosis aroused by high
glucose was also prevented considerably by
fasudil, a kind of pharmacological inhibitor of RhoA/ROCK1 pathway. These findings indicate that RhoA/ROCK1 signaling directly modulates MVED, suggesting a novel therapeutic target for DR.