Department of Biochemistry, Faculty of Veterinary Medicine, Suez Canal University, Ismailia, 41522, Egypt.
Department of Ophthalmology, Faculty of Medicine, Suez Canal University, Ismailia, 41522, Egypt.
Exp Eye Res. 2019 Sep;186:107742. doi: 10.1016/j.exer.2019.107742. Epub 2019 Jul 22.
Diabetic retinopathy (DR) is recognized as one of the leading causes of blindness worldwide. Searching and validation for a novel therapeutic strategy to prevent its progress are promising. This work aimed to assess the retinal protective effects of duloxetine (DLX) in Alloxan-induced diabetic mice model. Animals were equally and randomly divided to four groups (eight mice per group); group 1: is the control group, 2: diabetic group, 3&4: diabetic and after 9 weeks received DLX for 4 weeks (15 mg/kg and 30 mg/kg), respectively. Quantitative real-time PCR (qPCR) analysis revealed nerve growth factor (NGF), inducible nitric oxide synthase (iNOS) and transforming growth factor beta (TGF-β) genes upregulation in the diabetic group compared to controls. Also, increased retinal malondialdehyde (MDA) and the decline of reduced glutathione (GSH) levels were observed. The morphometric analysis of diabetic retina revealed a significant reduction in total retinal thickness compared to control. Diabetic retinal immunostaining and Western blot analyses displayed glial fibrillary acidic protein (GFAP) and vascular endothelial cell growth factor (VEGF) proteins expression upregulation as well as glucose transporter-1 (GLUT-1) downregulation comparing to controls. However, DLX-treated groups showed downregulated NGF, iNOS, and TGF-β that was more obviously seen in the DLX-30 mg/kg group than DLX-15 mg/kg group. Furthermore, these groups showed amelioration of the oxidative markers; MDA and GSH, retaining the total retinal thickness nearly to control, GFAP and VEGF downregulation, and GLUT-1 upregulation compared to diabetic group. Taken together, it could be summarized that duloxetine can attenuate DR via the anti-inflammatory and the anti-oxidative properties as well as modulating the angiogenic and the neurotrophic factors expressions. This could hopefully pave the road to be included in the novel list of the therapeutic regimen for DR after validation in the clinic.
糖尿病性视网膜病变（DR）是全球致盲的主要原因之一。寻找和验证新的治疗策略以阻止其进展是有希望的。本工作旨在评估度洛西汀（DLX）在链脲佐菌素诱导的糖尿病小鼠模型中的视网膜保护作用。动物等分为四组（每组 8 只）；1 组：对照组，2 组：糖尿病组，3 组和 4 组：糖尿病组，9 周后分别给予 DLX 治疗 4 周（15mg/kg 和 30mg/kg）。定量实时 PCR（qPCR）分析显示，与对照组相比，糖尿病组神经生长因子（NGF）、诱导型一氧化氮合酶（iNOS）和转化生长因子-β（TGF-β）基因上调。此外，还观察到视网膜丙二醛（MDA）增加和还原型谷胱甘肽（GSH）水平下降。糖尿病视网膜形态计量学分析显示，与对照组相比，总视网膜厚度明显减少。糖尿病视网膜免疫组化和 Western blot 分析显示，与对照组相比，胶质纤维酸性蛋白（GFAP）和血管内皮生长因子（VEGF）蛋白表达上调，葡萄糖转运蛋白-1（GLUT-1）表达下调。然而，DLX 治疗组显示 NGF、iNOS 和 TGF-β 下调，DLX-30mg/kg 组比 DLX-15mg/kg 组更为明显。此外，这些组显示氧化标记物 MDA 和 GSH 得到改善，总视网膜厚度接近对照组，GFAP 和 VEGF 下调，GLUT-1 上调，与糖尿病组相比。综上所述，度洛西汀可通过抗炎、抗氧化作用以及调节血管生成和神经营养因子的表达来减轻 DR。这有望为 DR 的治疗方案开辟新的道路，在临床验证后纳入新的治疗方案。
