Department of Ophthalmology, Affiliated Hospital of Nantong University, Nantong, China.
Department of Ophthalmology, Affiliated Hospital 2 of Nantong University, Nantong, China.
Biochem Biophys Res Commun. 2021 Jul 5;561:143-150. doi: 10.1016/j.bbrc.2021.05.027. Epub 2021 May 21.
Retinal pigment epithelium (RPE) cell damage, including mitophagy-associated cell apoptosis, accelerates the pathogenesis of diabetic retinopathy (DR), a common complication of diabetes that causes blindness. Müller cells interact with RPE cells via pro-inflammatory cytokines, such as tumor necrosis factor α (TNF-α). Herein, we investigated the role of the RPE cell epidermal growth factor receptor (EGFR)/p38 mitogen-activated protein kinase (p38)/nuclear factor kappa B (NF-κB) pathway in Müller cell-derived TNF-α-induced mitophagy-associated apoptosis during DR. Our results showed that TNF-α released from Müller cells activated the EGFR/p38/NF-κB/p62 pathway to increase mitophagy and apoptosis in RPE cells under high glucose (HG) conditions. Additionally, blockade of the TNF-α/EGFR axis alleviates blood-retina barrier breakdown in diabetic mice. Our data further illustrate the effects of the Müller cell inflammatory response on RPE cell survival, implying potential molecular targets for DR treatment.
视网膜色素上皮 (RPE) 细胞损伤，包括与细胞自噬相关的细胞凋亡，加速了糖尿病性视网膜病变 (DR) 的发病机制，这是糖尿病的常见并发症，可导致失明。Müller 细胞通过促炎细胞因子，如肿瘤坏死因子 α (TNF-α) 与 RPE 细胞相互作用。在此，我们研究了在 DR 过程中，Müller 细胞衍生的 TNF-α诱导的与自噬相关的 RPE 细胞凋亡中 RPE 细胞表皮生长因子受体 (EGFR)/p38 丝裂原激活蛋白激酶 (p38)/核因子 kappa B (NF-κB) 通路的作用。我们的结果表明，Müller 细胞释放的 TNF-α激活了 EGFR/p38/NF-κB/p62 通路，在高糖 (HG) 条件下增加了 RPE 细胞的自噬和凋亡。此外，阻断 TNF-α/EGFR 轴可减轻糖尿病小鼠的血视网膜屏障破坏。我们的数据进一步说明了 Müller 细胞炎症反应对 RPE 细胞存活的影响，这暗示了 DR 治疗的潜在分子靶点。
