Donepezil (DNPZ) has shown neuroprotective effect in many disorders. The current study tested the putative retinoprotection provided by donepezil in mouse diabetic retinopathy. Swiss albino mice were allocated to, 1] saline control, 2] diabetic, 3&4] diabetic+DNPZ (1 or 4 mg/kg). After induction of diabetes, mice were maintained for 8 weeks then DNPZ therapy was launched for 28 days. Retinas were isolated and used for histopathology and immunohistochemistry for caspase 3 and the anti-apoptotic protein, B-cell lymphoma 2 (BCl2). Retinas were examined for glutamate, acetylcholine and oxidation markers. Western blot analysis measured inflammatory cytokines, N-methyl-d-aspartate receptors (NMDARs), phosphorylated and total phosphatidylinositol-3 kinase and mTOR, BCl2 and cleaved caspase 3. Significant histopathological changes and decreased thickness were found in diabetic retinas (125.52 ± 2.85 vs. 157.15 ± 7.55 in the saline group). In addition, retinal glutamate (2.39-fold), inflammatory cytokines and NMDARs proteins (4.9-fold) were higher in the diabetic retinas. Western blot analysis revealed low ratio of phosphorylated/total PI3K (0.21 ± 0.043 vs. 1 ± 0.005) and mTOR (0.18 ± 0.04 vs. 1 ± 0.005), low BCl2 (0.28 ± 0.06 vs. 1 ± 0.005) and upregulated cleaved caspase 3 (5.18 ± 1.27 vs. 1 ± 0.05 in the saline group) versus the saline control. DNPZ ameliorated the histopathologic manifestations and to prevent the decrease in retinal thickness. DNPZ (4 mg/kg) improved phosphorylation of PI3K (0.76 ± 0.12 vs. 0.21 ± 0.04) and mTOR (0.59 ± 0.09 vs. 0.18 ± 0.04) and increased BCl2 (0.75 ± 0.08 vs. 0.28 ± 0.06) versus the diabetic control group. This study explained the retinoprotective effect of DNPZ in mouse diabetic retinopathy and highlighted that mitigation of excitotoxicity, improving phosphorylation of PI3K/mTOR and increasing BCl2 contribute to this effect.

多奈哌齐（DNPZ）在许多疾病中均显示出神经保护作用。目前的研究测试了多奈哌齐在小鼠糖尿病性视网膜病中提供的假定的视网膜保护作用。将瑞士的白化病小鼠分为1]生理盐水对照组，2]糖尿病，3＆4]糖尿病+ DNPZ（1或4 mg / kg）。诱发糖尿病后，将小鼠维持8周，然后开始DNPZ治疗28天。分离出视网膜并将其用于胱天蛋白酶3和抗凋亡蛋白B细胞淋巴瘤2（BCl2）的组织病理学和免疫组化。检查视网膜的谷氨酸，乙酰胆碱和氧化标记。Western印迹分析测定炎症细胞因子，N-甲基-d-天冬氨酸受体（NMDARs），磷酸化和总磷脂酰肌醇3激酶以及mTOR，BCl2和裂解的半胱氨酸蛋白酶3。在糖尿病视网膜中发现了显着的组织病理学改变和厚度降低（盐水组为125.52±2.85 vs. 157.15±7.55）。另外，糖尿病视网膜中的视网膜谷氨酸（2.39倍），炎性细胞因子和NMDARs蛋白（4.9倍）更高。Western印迹分析显示磷酸化/总PI3K的比例低（0.21±0.043 vs. 1±0.005）和mTOR（0.18±0.04 vs. 1±0.005），低BCl2（0.28±0.06 vs. 1±0.005）和裂解的胱天蛋白酶上调3（与生理盐水对照组相比，为5.18±1.27 vs. 1±0.05）。DNPZ改善了组织病理学表现，并防止了视网膜厚度的减少。DNPZ（4 mg / kg）改善了PI3K的磷酸化（0.76±0.12 vs.0。与糖尿病对照组相比，mTOR（21±0.04）和mTOR（0.59±0.09 vs.0.18±0.04）和BCl2升高（0.75±0.08 vs.0.28±0.06）。这项研究解释了DNPZ在小鼠糖尿病性视网膜病中的视网膜保护作用，并强调了减轻兴奋性毒性，改善PI3K / mTOR的磷酸化作用以及增加BCl2的作用。