tacrolimus and Diabetic-Retinopathy

In the first five yr after liver transplant, approximately one in 10 pediatric recipients will develop NODAT. Factors associated with higher risk for NODAT have been difficult to identify due to lack of uniformity in reporting and data collection. Limited studies have reported higher risk in those who are at an older age at transplant, those with high-risk ethnic backgrounds, and in those with particular underlying conditions, such as CF and primary sclerosing cholangitis. Immunosuppressive medications, including tacrolimus, cyclosporine A, GC, and sirolimus, have been implicated as contributing to NODAT, to varying degrees. Identifying those at highest risk, appropriately screening, and diagnosing NODAT is critical to initiating timely treatment and avoiding potential complications. In the pediatric population, treatment is limited primarily to insulin, with some consideration for metformin. Children with NODAT should be monitored carefully for complications of DM, including microalbuminuria, hypertension, hyperlipidemia, and retinopathy.

Topics: Albuminuria; Child; Cyclosporine; Diabetes Mellitus; Diabetic Retinopathy; Glucocorticoids; Humans; Hyperlipidemias; Hypertension; Immunosuppressive Agents; Insulin; Liver Failure; Liver Transplantation; Metformin; Pediatrics; Risk Factors; Sirolimus; Tacrolimus

Topics: Administration, Topical; Adrenal Cortex Hormones; Aged; Antimalarials; Calcineurin Inhibitors; Carcinoma, Squamous Cell; Clofazimine; Diabetic Retinopathy; Drug Therapy, Combination; Ear; Humans; Leprostatic Agents; Lupus Erythematosus, Discoid; Lymph Node Excision; Male; Middle Aged; Neoplasm Staging; Skin Neoplasms; Tacrolimus; Treatment Outcome

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.

Topics: Animals; Diabetes Mellitus, Experimental; Diabetic Retinopathy; Gene Expression Regulation; Immunosuppressive Agents; Male; Mice; Mice, Inbred C57BL; NF-kappa B; Random Allocation; Retina; Tacrolimus