Histone deacetylase 3 inhibitor attenuates diabetic retinopathy in mice.

Abstract

Diabetic retinopathy is one of the most common microvascular complications of diabetes. Inhibition of histone deacetylase 3 (Hdac3) was proven to be a successful way to ameliorate central nervous system injury and vision problem in a glaucoma mouse model. However, its role in diabetic retinopathy remains largely unknown. Eight-week-old C57BL/6J mice were intraperitoneally injected with 50 mg of streptozotocin for 5 consecutive days to induce diabetes. After 1 wk, diabetic mice were selected and treated with Hdac3 inhibitor RGFP966 once every 3 days for 12 consecutive weeks. It was found that RGFP966 could decrease the mRNA and protein expression of Hdac3. It significantly increased diabetic retinopathy-reduced retinal thickness without affecting fasting blood glucose. It also decreased diabetic retinopathy-activated oxidative stress and cell apoptosis. Moreover, diabetic retinopathy mice displayed an increased expression of vascular endothelial growth factor and a decreased expression of glial fibrillary acidic protein, both of which were partially restored by RGFP966 treatment. Mechanically, RGFP966 decreased the expression of NADPH oxidase 2 (Nox2) whereas it increased the expression of superoxide dismutase 2 (Sod2) in diabetic retinopathy mice. In conclusion, RGFP966 significantly reduces oxidative stress, inflammation, and cell apoptosis in the retina of streptozotocin-induced diabetic mice, which may be associated with its modulation of Nox2 and Sod2 expression.NEW & NOTEWORTHY The study demonstrated that RGFP966 significantly reduced oxidative stress, inflammation, and cell apoptosis in the retina of streptozotocin-induced diabetic mice, which may be associated with Nox2 and Sod2 expression.