Department of Ophthalmology, Renmin Hospital of Wuhan University, Hubei, China.
Nanchang University School of Ophthalmology & Optometry, Nanchang, China.
Exp Eye Res. 2021 Aug;209:108683. doi: 10.1016/j.exer.2021.108683. Epub 2021 Jun 25.
Resveratrol (RES) is a natural polyphenol that has been shown to protect retinal ganglion cells (RGCs) following retinal ischemia reperfusion (I/R) injury. However, the molecular mechanisms of resveratrol function are yet to be fully elucidated. Thus, this study explored the potential mechanisms of resveratrol in vivo.
A retinal ischemia reperfusion injury model was established in adult male C57BL/6 J mice. Intraperitoneal injection of resveratrol was administered continuously for 5 days. RGC survival was determined by immunofluorescence staining with Brn3a. Flash electroretinography (ERG) was conducted to assess visual function. Proteins of HIF-1a, VEGF, p38, p53, PI3K, Akt, Bax, Bcl2, and Cleaved Caspase3 were detected using Western blot.
RES administration significantly ameliorated retinal thickness damage and increased Brn3a stained RGCs 7 days after I/R injury. We also found that administration of RES remarkably inhibited the upregulation of mitochondrial apoptosis-related protein Bax and Cleaved Caspase3, as well as increased the expression of Bcl2. Furthermore, RES administration significantly suppressed the I/R injury-induced upregulation of the HIF-1a/VEGF and p38/p53 pathways, while activating the I/R injury-induced downregulation of the PI3K/Akt pathway. Moreover, RES administration remarkably improved retinal function after I/R injury-induced functional impairment.
Our data demonstrated that resveratrol can mitigate retinal ischemic injury induced RGC loss and retinal function impairment by inhibiting the HIF-1a/VEGF and p38/p53 pathways while activating the PI3K/Akt pathway. Therefore, our results further reinforce that resveratrol has potential for treating glaucoma.
白藜芦醇（RES）是一种天然多酚，已被证明可在视网膜缺血再灌注（I/R）损伤后保护视网膜神经节细胞（RGC）。然而，RES 的作用机制尚未完全阐明。因此，本研究探讨了 RES 在体内的潜在作用机制。
建立成年雄性 C57BL/6J 小鼠视网膜缺血再灌注损伤模型。连续腹腔注射 RES 5 天。用 Brn3a 免疫荧光染色检测 RGC 存活。闪光视网膜电图（ERG）评估视觉功能。Western blot 检测 HIF-1a、VEGF、p38、p53、PI3K、Akt、Bax、Bcl2 和 Cleaved Caspase3 蛋白。
RES 给药可显著改善 I/R 损伤后 7 天的视网膜厚度损伤并增加 Brn3a 染色的 RGC。我们还发现，RES 给药可显著抑制线粒体凋亡相关蛋白 Bax 和 Cleaved Caspase3 的上调，并增加 Bcl2 的表达。此外，RES 给药可显著抑制 I/R 损伤诱导的 HIF-1a/VEGF 和 p38/p53 通路的上调，同时激活 I/R 损伤诱导的 PI3K/Akt 通路的下调。此外，RES 给药可显著改善 I/R 损伤引起的视网膜功能障碍后的视网膜功能。
我们的数据表明，RES 可通过抑制 HIF-1a/VEGF 和 p38/p53 通路同时激活 PI3K/Akt 通路来减轻视网膜缺血性损伤诱导的 RGC 丢失和视网膜功能障碍，因此，我们的结果进一步证实 RES 具有治疗青光眼的潜力。
