Abstract：
Glaucoma is an eye disease with a high rate of blindness and a complex pathogenesis. Ocular hypertension (OHT) is a critical risk factor, and retinal ischemia/reperfusion (I/R) is an important pathophysiological basis. This study was designed to investigate the retinal neuroprotective effect of oral naringenin in an acute retinal I/R model and a chronic OHT model and the possible mechanism involved. After the I/R and OHT models were established, mice were given vehicle or naringenin (100 mg/kg or 300 mg/kg). Hematoxylin-eosin (HE) staining and immunostaining of RBPMS and glial fibrillary acidic protein (GFAP) were used to evaluate retinal injury. GFAP, CD38, Sirtuin1 (SIRT1), and NOD-like receptor protein 3 (NLRP3) expression levels were measured by Western blotting. In the OHT model, intraocular pressure (IOP) was dynamically maintained at approximately 20-25 mmHg after injury. The retinal structure was damaged, and retinal ganglion cells (RGCs) were lost in both models. Naringenin ameliorated the abovementioned indications but also demonstrated that high concentrations of naringenin significantly inhibited retinal astrocyte activation and inhibited damage-induced increases in the expression of GFAP, NLRP3, and CD38 proteins, while SIRT1 protein expression was upregulated. This study showed for the first time that naringenin can reduce microbead-induced IOP elevation in the OHT model, providing new evidence for the application of naringenin in glaucoma. Naringenin may mediate the CD38/SIRT1 signaling pathway, inhibit astrocyte activation, and ultimately exert an anti-inflammatory effect to achieve retinal neuroprotection.
摘要：
青光眼是一种致盲率高、发病机制复杂的眼病。眼部高血压（OHT）是一个关键的危险因素，视网膜缺血/再灌注(I/R)是视网膜缺血/再灌注的重要病理生理基础。本研究旨在探讨口服柚皮素在急性视网膜I/R模型和慢性OHT模型中的视网膜神经保护作用及其可能的机制。在建立I/R和OHT模型后，给小鼠服用赋形剂或柚皮素（100mg/kg或300mg/kg）。采用苏木精-伊红(HE)染色、RBPMS和胶质纤维酸性蛋白(GFAP)免疫染色评价视网膜损伤。GFAP,CD38,Sirtuin1(SIRT1),用蛋白质印迹法测定NOD样受体蛋白3(NLRP3)的表达水平。在OHT模型中,损伤后眼内压(IOP)动态维持在约20~25mmHg.视网膜结构受损,和视网膜神经节细胞（RGC）在两个模型中都丢失。柚皮素改善了上述适应症，但也证明了高浓度的柚皮素显著抑制视网膜星形胶质细胞活化，抑制损伤诱导的GFAP表达增加，NLRP3和CD38蛋白，而SIRT1蛋白表达上调。这项研究首次表明柚皮素可以降低OHT模型中微珠诱导的IOP升高，为柚皮素在青光眼中的应用提供了新的证据。柚皮素可能介导CD38/SIRT1信号通路,抑制星形胶质细胞激活，并最终发挥抗炎作用实现视网膜神经保护。
