视网膜神经退行性疾病,包括高血压视网膜病变,涉及视网膜神经元的进行性损伤,导致视力障碍。在这项研究中,我们研究了自发性高血压大鼠(SHR)视网膜神经变性的病理机制,使用WistarKyoto(WKY)大鼠作为正常血压对照。我们观察到SHR表现出明显更高的血压和减少的视网膜厚度,显示视网膜神经变性.分子检测包括定量实时聚合酶链反应,免疫印迹,免疫荧光染色显示促炎细胞因子肿瘤坏死因子-α水平升高,凋亡标志物(Fas,FasL,caspase-8,活性caspase-3和裂解的聚(ADP-核糖)聚合酶),和SHR视网膜中的坏死标记(受体相互作用蛋白激酶-1和-3)。此外,我们发现SHR的视网膜色素上皮(RPE)中转化生长因子-β(TGF-β)水平升高,随着卵磷脂视黄醇酰基转移酶(LRAT)的减少,调节类维生素A代谢和感光体健康。在人RPE细胞(ARPE-19)中,TGF-β给药抑制LRAT的mRNA和蛋白质水平;和vactosertib,TGF-β受体激酶1型的选择性抑制剂逆转了TGF-β的作用。这些结果表明,高血压引起的视网膜神经变性涉及炎症,凋亡,坏死,破坏类维生素A代谢,为高血压视网膜病变提供潜在的治疗靶点。
Retinal neurodegenerative diseases, including hypertensive retinopathy, involve progressive damage to retinal neurons, leading to visual impairment. In this study, we investigated the pathological mechanisms underlying retinal neurodegeneration in spontaneously hypertensive rats (SHR), using Wistar Kyoto (WKY) rats as normotensive controls. We observed that SHR exhibited significantly higher blood pressure and decreased retinal thickness, indicating retinal neurodegeneration. Molecular tests including quantitative real-time polymerase chain reaction, immunoblot, and immunofluorescent staining showed elevated levels of the pro-inflammatory cytokine tumor necrosis factor-α, apoptotic markers (Fas, FasL, caspase-8, active caspase-3, and cleaved poly (ADP-ribose) polymerase), and necroptotic markers (receptor-interacting protein kinase-1 and -3) in SHR retinas. Additionally, we found elevated transforming growth factor-β (TGF-β) levels in the retinal pigment epithelium (RPE) of SHR, with a decrease in lecithin retinol acyltransferase (LRAT), which regulates retinoid metabolism and
photoreceptor health. In human RPE cells (ARPE-19), TGF-β administration suppressed mRNA and protein levels of LRAT; and vactosertib, a selective inhibitor of TGF-β receptor kinase type 1, reversed the effect of TGF-β. These findings suggest that hypertension-induced retinal neurodegeneration involves inflammation, apoptosis, necroptosis, and disrupted retinoid metabolism, providing potential therapeutic targets for hypertensive retinopathy.