FK506 alleviates blood-retinal barrier breakdown and reduces retinal vascular permeability in early streptozotocin-induced diabetic rat

Objective: Diabetic retinopathy is a complex disease that potentially involves inflammation in its pathogenesis. It has been demonstrated that FK506, one of its potent immunosuppressive agents, possess anti-inflammatory properties. Therefore, the present study aimed to explore whether FK506 could reduce vascular damage in experimental diabetic retinopathy. Methods: The streptozotocin-induced model of diabetes was established using Wistar rats. Animals received single intravitreal injections of FK506 or vehicle after seven days. The blood retinal barrier (BRB) was determined using Evans blue permeation, leukostasis was determined using Fluorescein-isothiocyanate (FITC)-coupled Concanavalin A lectin, and the expression of VEGF and ICAM-1 was detected by western blot. Results: Intravitreal delivery of FK506 protects BRB integrity against vascular leakage by inhibiting diabetic retinal leukocyte adhesion to retinal vessels and downregulating the expression of VEGF during early diabetes. Twenty-four hours after FK506 treatment, VEGF decreased by 82.17%, compared with diabetic rats without treatment (P < 0.01). In addition, FK506 inhibited the expression of ICAM-1, a significant inflammation protein. Moreover, ICAM-1 decreased by 74.27% after treatment with 2.5 ng of FK506, when compared with diabetic animals without treatment (P < 0.01). Conclusion: FK506 could inhibit the degree of retinal inflammation and attenuate neovascularization in early diabetic mice. The topical application of FK506 appears as a highly promising novel approach for the treatment of diabetic retinopathy.