Nogo receptor knockdown and ciliary neurotrophic factor attenuate diabetic retinopathy in streptozotocin-induced diabetic rats.

Abstract

Diabetic retinopathy (DR) is a common complication of diabetes mellitus (DM). We investigated whether Nogo receptor (NgR) knockdown and ciliary neurotrophic factor (CNTF) treatment, either alone or in combination, ameliorated diabetic retinopathy (DR) in diabetic rat model. STZ-induced diabetic rats were administrated for a total of 12 weeks with 3 µM siRNA (5 µl) once every 6 weeks and/or 1 µg CNTF weekly. The retinal tissues were excised. We measured cell number in ganglion cell layer (GCL) using H&E staining and cell apoptosis using TUNEL assay. Bax, Bcl-2, Caspase-3, F-actin, GAP-43, NgR, RhoA and Rock1 levels were then analyzed by Western blotting, Immunohistochemistry or Real-time PCR. We found that NgR siRNA or CNTF injection alone significantly increased cell count in GCL in diabetic rats, inhibited ganglion cell apoptosis, elevated Bcl-2, F-actin and GAP-43, and decreased Bax, Caspase-3, NgR, RhoA and Rock1 levels. Combination treatment further prevented retinal ganglion cell loss, enhanced growth cone cytoskeleton and axonal regeneration, and suppressed NgR/RhoA/Rock1. Our results indicate that combination therapy has therapeutic potential for the treatment of DR.