糖尿病網膜症治療標的としてのROCK
スポンサーリンク
概要
- 論文の詳細を見る
Despite considerable recent advances in vitreoretinal surgery, generally performed for more advanced stages of diabetic retinopathy (DR), satisfactory visual acuity cannot always be achieved. New approaches for amelioration and treatment of DR are thus urgently needed. In the early stages of DR, leukocyte adhesion in the retinal microvasuculature substantially contributes to DR. We investigated the involvement of the Rho/ROCK pathway in diabetic microvasculopathy and the therapeutic potential of fasudil, a selective ROCK inhibitor, and demonstrated that the Rho/ROCK pathway plays a critical role in leukocyte adhesion in diabetic retinal microvasuculature and endothelial damage. Fasudil protects the vascular endothelium at least in part by inhibiting neutrophil adhesion and reducing neutrophil-induced endothelial injury via endothelial nitric oxide. In the later stages of DR, namely proliferative diabetic retinopathy, tractional retinal detachment associated with a cicatrical contraction of proliferative membranes can cause severe vision loss. We demonstrated the possible involvement of hyalocytes in proliferative membrane formation and its contraction mainly mediated through the function of TGF-β2 resulting in myofibroblastic transdifferentiation and phosphorylation of the myosin light chain, a downstream mediator of ROCK. ROCK inhibition by fasudil or statins successfully inhibited cicatrical contraction of the proliferative membranes both in vitro and in vivo. Further studies for direct evidence demonstrating the therapeutic potential of ROCK inhibition in clinical studies could provide new avenues of intervention designed to inhibit DR.
- 福岡歯科大学学会の論文
- 2010-12-31