Aquaporin-4 triggers inflammation in a murine endotoxin-induced uveitis (EIU) model

Abstract

Abstract Introduction This study aimed to identify the role of aquaporin‑4 (AQP4) in uveitis, and screen for a novel therapeutic target of potential. Methods 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). Results 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. Conclusion 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.

Keywords

• Aquaporin‑4 (AQP4)
• Endotoxin-induced uveitis (EIU)
• Inflammation
• Inflammatory factors