Diabetic retinopathy (DR) is a neurovascular complication of diabetes, driven by an intricate network of cellular and molecular mechanisms. This study sought to explore the mechanisms by investigating the role of 12-hydroxyeicosatetraenoic acid (12-HETE), its receptor GPR31, and microRNA (miR-29) in the context of DR, specifically focusing on their impact on Müller glial cells. We found that 12-HETE activates Müller cells (MCs), elevates glutamate production, and induces inflammatory and oxidative responses, all of which are instrumental in DR progression. The expression of GPR31, the receptor for 12-HETE, was prominently found in the retina, especially in MCs and retinal ganglion cells, and was upregulated in diabetes. Interestingly, miR29 showed potential as a protective agent, mitigating the harmful effects of 12-HETE by attenuating inflammation and oxidative stress, and restoring the expression of pigment epithelium-derived factor (PEDF). Our results underline the central role of 12-HETE in DR progression through activation of a neurovascular toxic pathway in MCs and illuminate the protective capabilities of miR-29, highlighting both as promising therapeutic targets for the management of DR.

糖尿病视网膜病变 (DR) 是糖尿病的一种神经血管并发症，由复杂的细胞和分子机制网络驱动。本研究试图通过研究 12-羟基二十碳四烯酸 (12-HETE)、其受体 GPR31和 microRNA (miR-29) 在 DR 中的作用来探索其机制，特别关注它们对 Müller胶质细胞的影响。我们发现 12-HETE 可以激活穆勒细胞 (MC)、提高谷氨酸产量并诱导炎症和氧化反应，所有这些都有助于 DR 的进展。GPR31（12-HETE 的受体）的表达主要存在于视网膜中，尤其是在 MC 和视网膜神经节细胞中，并且在糖尿病中表达上调。有趣的是，miR29 显示出作为保护剂的潜力，通过减轻炎症和氧化应激来减轻 12-HETE 的有害影响，并恢复色素上皮衍生因子 (PEDF) 的表达。我们的结果强调了 12-HETE 通过激活 MC 中的神经血管毒性途径在 DR 进展中的核心作用，并阐明了 miR-29 的保护能力，强调两者都是治疗 DR 的有希望的治疗靶点。