Yuan Dongqing, Xu Yingnan, Xue Lian, Zhang Weiwei, Gu Liuwei, Liu Qinghuai
Department of Ophthalmology, Jiangsu Province Hospital, The First Affiliated Hospital with Nanjing Medical University, Jiangsu Women and Children Health Hospital, 300 Guangzhou Road, Nanjing, Jiangsu, 210029, China.
Department of Ophthalmology, The Affiliated Eye Hospital of Nanjing Medical University, Nanjing, China.
Heliyon. 2024 May 6;10(9):e30786. doi: 10.1016/j.heliyon.2024.e30786. eCollection 2024 May 15.
Oxidative stress-induced retinal neurodegenerative changes are among the pathological alterations observed in diabetic retinopathy. Resveratrol (RSV), a polyphenolic compound with diverse pharmacological effects, has shown preventive qualities in several neurodegenerative illnesses, including anti-inflammatory, anti-aging, and antioxidant benefits. However, its therapeutic efficacy in diabetic retinal neurodegeneration has not yet been thoroughly elucidated. Our study aimed to explore the protective mechanisms and therapeutic benefits of RSV on diabetic retinal neurodegeneration alterations.
Using streptozotocin, we created a diabetic mouse model and conducted visual electrophysiological examinations on mice from the normal group, diabetic group, and diabetic group treated with RSV. Retinas were harvested for histological staining. Additionally, primary retinal ganglion cells cultured in high glucose conditions were used to assess malondialdehyde (MDA) levels and superoxide dismutase (SOD) levels upon siRNA-mediated nuclear factor erythroid 2-related factor 2 (Nrf2) interference. Protein levels of Nrf-2, heme oxygenase-1 (HO-1), and transcriptional levels of them were also measured.
We demonstrated that RSV significantly improved the retinal morphology and function in the diabetic retinopathy model mice. The treated mice exhibited notable improvements in visual electrophysiology, with a significant reduction in retinal ganglion cell apoptosis. Following RSV treatment, the high glucose-cultured ganglion cells demonstrated a considerable rise in SOD levels and a substantial drop in MOD. Moreover, the protein expression of solute carrier family 7 member 11 (SLC7A11) and Nrf2 significantly increased. RT-PCR and Western blot results indicated a significant attenuation of RSV's therapeutic effects upon Nrf2 inhibition.
Our findings suggest that RSV may reduce oxidative stress levels in the retina and inhibit retinal ganglion cell apoptosis via reducing the Nrf2/HO-1 pathway, which lessens the harm that excessive glucose causes to the retina.
氧化应激诱导的视网膜神经退行性变化是糖尿病视网膜病变中观察到的病理改变之一。白藜芦醇（RSV）是一种具有多种药理作用的多酚类化合物，在包括抗炎、抗衰老和抗氧化等多种神经退行性疾病中显示出预防作用。然而，其在糖尿病视网膜神经退行性变中的治疗效果尚未得到充分阐明。我们的研究旨在探讨RSV对糖尿病视网膜神经退行性变改变的保护机制和治疗益处。
使用链脲佐菌素建立糖尿病小鼠模型，并对正常组、糖尿病组和RSV治疗的糖尿病组小鼠进行视觉电生理检查。摘取视网膜进行组织学染色。此外，使用在高糖条件下培养的原代视网膜神经节细胞，评估小干扰RNA（siRNA）介导的核因子红细胞2相关因子2（Nrf2）干扰后丙二醛（MDA）水平和超氧化物歧化酶（SOD）水平。还测量了Nrf-2、血红素加氧酶-1（HO-1）的蛋白水平及其转录水平。
我们证明RSV显著改善了糖尿病视网膜病变模型小鼠的视网膜形态和功能。治疗后的小鼠在视觉电生理方面有显著改善，视网膜神经节细胞凋亡明显减少。RSV治疗后，高糖培养的神经节细胞SOD水平显著升高，MOD显著下降。此外，溶质载体家族7成员11（SLC7A11）和Nrf2的蛋白表达显著增加。逆转录聚合酶链反应（RT-PCR）和蛋白质印迹结果表明，Nrf2抑制后RSV的治疗效果显著减弱。
我们的研究结果表明，RSV可能通过降低Nrf2/HO-1途径来降低视网膜氧化应激水平并抑制视网膜神经节细胞凋亡，从而减轻过量葡萄糖对视网膜造成的损害。
