Tacrolimus (FK506) prevents early retinal neovascularization in streptozotocin-induced diabetic mice

Diabetic retinopathy is a complex disease that has potential involvement of inflammatory in its pathogenesis. We hypothesized that tacrolimus (FK506), one of the potent immunosuppressive agent, could be effective against diabetic retinopathy, which involves significant inflammation. The aim of the present study was to investigate the effects of FK506 in early retinal changes of streptozotocin-induced diabetic mice. The effect of FK506 treatment (10 μg per eye for one week) was evaluated by TNF-a, VEGF, iNOS and COX-2 protein levels measurement, neovascularization, and the activation of NF-kB in the retina. Increased amounts of cytokines, neovascularization, inflammatory markers and activation of NF-kB were observed in retina from diabetic mice. FK506 treatment significantly lowered retinal TNF-a, VEGF, iNOS and COX-2. Further, treatment with FK506 significantly suppressed diabetes-related neovascularization, as well as the activation of NF-kB. These data demonstrated that FK506 attenuates the degree of retinal inflammation and preserving the neovascularization in early diabetic mice.