Wang Qiang, Gong Yajun, Ma Xinqi, Fu Xin, Li Ruobi, Qiu Kairui, Wang Yanbin, Zhao Qiulan, Li Ling, Huang Qian, Gao Longyang, Hu Xiongli, Zhou Xiaolai, Zhong Jingxiang
Department of Ophthalmology, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong Province, 510632, China.
Changde Hospital, Xiangya School of Medicine, Central South University (The First People's Hospital of Changde City), Changde, Hunan Province, 415000, China.
BMC Ophthalmol. 2025 Jul 1;25(1):372. doi: 10.1186/s12886-025-04192-8.
This study aimed to identify the role of aquaporin‑4 (AQP4) in uveitis, and screen for a novel therapeutic target of potential.
AQP4 knockout mice were applied in this study. The manifestations of mice oculi and inflammatory factors were monitored and compared between the conditions of wild-type and endotoxin-induced uveitis (EIU).
In the mouse retina, immunofluorescence showed that AQP4 is mainly expressed by Müller cells. The results showed that EIU caused obvious inflammatory reactions in the oculi of wild-type mice, including the ascendence of vitreous cells and thickened retinal layers, compared with the AQP4 knockout mice. According to the scoring criteria of the anterior segment, the ciliary congestion, hypopyon, posterior adhesion of iris, and anterior chamber cell counts were significantly deteriorated by EIU modeling, between which the AQP4 ablation attenuated the inflammation. Further investigations were performed to explore the information on inflammatory factors: The pro-inflammatory cytokines, IL-1β, IL-6, and TNF-α were increased in the mice oculi under EIU, while they were maintained in lower levels by AQP4 ablation; The inflammation regulatory agents, cd-20 and arg-1, were massively increased in the mice oculi by EIU modeling, while AQP4 ablation further enhanced their expression level.
AQP4 is a participant in EIU, where it promotes inflammation via reconstructing the balance of the ocular immune condition. The results of the current study highlight the potential of AQP4 to become a therapeutic target in the eyes for uveitis.
本研究旨在确定水通道蛋白4(AQP4)在葡萄膜炎中的作用,并筛选潜在的新型治疗靶点。
本研究采用AQP4基因敲除小鼠。监测并比较野生型和内毒素诱导性葡萄膜炎(EIU)条件下小鼠眼部表现及炎症因子。
在小鼠视网膜中,免疫荧光显示AQP4主要由 Müller 细胞表达。结果表明,与 AQP4 基因敲除小鼠相比,EIU 在野生型小鼠眼部引起明显的炎症反应,包括玻璃体细胞增多和视网膜层增厚。根据眼前节评分标准,EIU 建模使睫状充血、前房积脓、虹膜后粘连和前房细胞计数显著恶化,其中 AQP4 缺失减轻了炎症。进一步研究以探索炎症因子信息:促炎细胞因子 IL-1β、IL-6 和 TNF-α 在 EIU 条件下小鼠眼内升高,而 AQP4 缺失使其维持在较低水平;炎症调节因子 cd-20 和 arg-1 在 EIU 建模后小鼠眼内大量增加,而 AQP4 缺失进一步提高了它们的表达水平。
AQP4 参与 EIU,通过重建眼部免疫状态平衡促进炎症。本研究结果突出了 AQP4 成为葡萄膜炎眼部治疗靶点的潜力。