Guo Xiliang, Liu Xuezheng
Department of Human Anatomy, School of Basic Medical Sciences, Guangxi Medical University, Nanning, Guangxi 530021, P.R. China.
Mol Med Rep. 2017 Aug;16(2):2030-2036. doi: 10.3892/mmr.2017.6850. Epub 2017 Jun 23.
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.
糖尿病视网膜病变（DR）是糖尿病（DM）的常见并发症。我们研究了单独或联合敲低Nogo受体（NgR）和睫状神经营养因子（CNTF）治疗是否能改善糖尿病大鼠模型中的糖尿病视网膜病变（DR）。用链脲佐菌素诱导的糖尿病大鼠，每6周给予一次3µM siRNA（5µl），共给药12周，和/或每周给予1µg CNTF。切除视网膜组织。我们用苏木精-伊红染色测量神经节细胞层（GCL）中的细胞数量，并用TUNEL法检测细胞凋亡。然后通过蛋白质印迹法、免疫组织化学或实时聚合酶链反应分析Bax、Bcl-2、Caspase-3、F-肌动蛋白、GAP-43、NgR、RhoA和Rock1的水平。我们发现，单独注射NgR siRNA或CNTF可显著增加糖尿病大鼠GCL中的细胞计数，抑制神经节细胞凋亡，提高Bcl-2、F-肌动蛋白和GAP-43的水平，并降低Bax、Caspase-3、NgR、RhoA和Rock1的水平。联合治疗进一步预防了视网膜神经节细胞的丢失，增强了生长锥细胞骨架和轴突再生，并抑制了NgR/RhoA/Rock1。我们的结果表明，联合治疗对DR具有治疗潜力。
