Lysosomal degradation of retinal glial AQP4 following its internalization induced by acute ocular hypertension

• Published in: Neuroscience letters Vol. 516; no. 1; pp. 135 - 140
• Main Authors: Gan, Sheng-Wei, Ran, Jian-Hua, Chen, Hai, Ren, Zhong-Qin, Sun, Shan-Quan, Zhu, Shu-Juan, Lu, Wei-Tian, Xu, Jin, Zhang, Bo, Huang, Juan, Wang, Ke-Jian, Chen, Zhen
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier Ireland Ltd 10.05.2012
• Subjects: Acute Disease; Animals; Aquaporin 4; Aquaporin 4 - metabolism; Aquaporins; Cells, Cultured; Endosome; Female; Glial; Hypertension; Immunofluorescence; Injuries; Internalization; Ischemia; LAMP-1 protein; Lysosome; Lysosomes; Lysosomes - metabolism; Mannose-6-phosphate receptors; Nervous system; Neuroglia - metabolism; Ocular Hypertension - metabolism; Protein degradation; Rats; Rats, Sprague-Dawley; Reperfusion; Retina; Retina - cytology; Retina - metabolism; Protein degradation; Aquaporin-4; Glial; Endosome; Internalization; Lysosome
• ISSN: 0304-3940; 1872-7972; 1872-7972
• DOI: 10.1016/j.neulet.2012.03.075

► AQP4 is internalized in the ischemic-reperfused rat retina. ► Lysosome is involved in degradation of internalized AQP4 in the reperfusion duration retina. ► Lysosomal target of AQP4 is potentially therapeutic targets for retinal edema. The membrane-bound water channel aquaporin-4 plays a significant role in the regulation of water movement within the retina. In retinal ischemia–reperfusion injury, changes in the expression and localization of aquaporin-4 have been reported. Previous studies also suggest that the internalization of several membrane-bound proteins, including aquaporin-4, may occur with or without lysosomal degradation. In this study, the internalization of aquaporin-4 was detected in the ischemic rat retina via double immunofluorescence labeling. Specifically, both aquaporin-4 and the mannose-6-phosphate receptor co-localized post-ischemic injury (10, 30 and 60min). The same results were found during a 12-h reperfusion window (2, 4 and 8h, respectively) following 60min of ischemia. Moreover, the co-expression of aquaporin-4 and lysosomal-associated membrane protein-1 was observed at 1–12h of reperfusion, with co-expression increasing followed by a gradual decrease. These combined findings suggest that AQP4 is internalized in the ischemic-reperfused retina, and the lysosome is involved in degrading the internalized aquaporin-4 during the reperfusion phase. Both the internalization of aquaporin-4 and its lysosomal degradation may serve as valuable therapeutic targets for managing ischemic-reperfused retinal injury.