title: Lysosomal degradation of retinal glial AQP4 following its internalization induced by acute ocular hypertension.
abstract: 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 60 min). The same results were found during a 12-h reperfusion window (2, 4 and 8 h, respectively) following 60 min of ischemia. Moreover, the co-expression of aquaporin-4 and lysosomal-associated membrane protein-1 was observed at 1-12 h 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.
authors.affiliation: Institute of Neuroscience, Chongqing Medical University, Chongqing 400016, PR China.
authors.forename: Sheng-Wei
authors.initials: SW
authors.lastname: Gan
authors.forename: Jian-Hua
authors.initials: JH
authors.lastname: Ran
authors.forename: Hai
authors.initials: H
authors.lastname: Chen
authors.forename: Zhong-Qin
authors.initials: ZQ
authors.lastname: Ren
authors.forename: Shan-Quan
authors.initials: SQ
authors.lastname: Sun
authors.forename: Shu-Juan
authors.initials: SJ
authors.lastname: Zhu
authors.forename: Wei-Tian
authors.initials: WT
authors.lastname: Lu
authors.forename: Jin
authors.initials: J
authors.lastname: Xu
authors.forename: Bo
authors.initials: B
authors.lastname: Zhang
authors.forename: Juan
authors.initials: J
authors.lastname: Huang
authors.forename: Ke-Jian
authors.initials: KJ
authors.lastname: Wang
authors.forename: Zhen
authors.initials: Z
authors.lastname: Chen
mesh_terms: D000208:Acute Disease; D000818:Animals; D051401:Aquaporin 4 / Q000378:metabolism*; D002478:Cells, Cultured; D005260:Female; D008247:Lysosomes / Q000378:metabolism*; D009457:Neuroglia / Q000378:metabolism*; D009798:Ocular Hypertension / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012160:Retina / Q000166:cytology / Q000378:metabolism*
chemical_list: C496030:AQP4 protein, human; D051401:Aquaporin 4