Journal article
Aquaporin 11 alleviates retinal Muller intracellular edema through water efflux in diabetic retinopathy
PHARMACOLOGICAL RESEARCH, v 187, 106559
Jan 2023
PMID: 36403720
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Retinal Muller glial dysfunction and intracellular edema are important mechanisms leading to diabetic macular edema (DME). Aquaporin 11 (AQP11) is primarily expressed in Muller glia with unclear functions. This study aims to explore the role of AQP11 in the pathogenesis of intracellular edema of Muller glia in diabetic reti-nopathy (DR). Here, we found that AQP11 expression, primarily located at the endfeet of Muller glia, was down -regulated with diabetes progression, accompanied by intracellular edema, which was alleviated by intravitreal injection of lentivirus-mediated AQP11 overexpression. Similarly, intracellular edema of hypoxia-treated rat Muller cell line (rMC-1) was aggravated by AQP11 inhibition, while attenuated by AQP11 overexpression, accompanied by enhanced function in glutamate metabolism and reduced cell death. The down-regulation of AQP11 was also verified in the Muller glia from the epiretinal membranes (ERMs) of proliferative DR (PDR) patients. Mechanistically, down-regulation of AQP11 in DR was mediated by the HIF-1 alpha-dependent and inde-pendent miRNA-AQP11 axis. Overall, we deciphered the AQP11 down-regulation, mediated by miRNA-AQP11 axis, resulted in Muller drainage dysfunction and subsequent intracellular edema in DR, which was partially reversed by AQP11 overexpression. Our findings propose a novel mechanism for the pathogenesis of DME, thus targeting AQP11 regulation provides a new therapeutic strategy for DME.
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Details
- Title
- Aquaporin 11 alleviates retinal Muller intracellular edema through water efflux in diabetic retinopathy
- Publication Details
- PHARMACOLOGICAL RESEARCH, v 187, 106559
- Publisher
- ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD; LONDON
- Grant note
- This study was supported by the National Natural Science Foundation of China (82171062, 81970810), the Science and Technology Commission of Shanghai Municipality (18411953400, 19495800700), National Key Basic Research Program of China (2017YFA0104100), and National Major Scientific and Technological Special Project for Significant New Drugs Development during the Thirtieth Five-year Plan Period (2019ZX09301113).; We also acknowledge the support from the Laboratory of Clinical and Visual Sciences (LCVS), Tongji Eye Institute, Tongji University School of Medicine, Shanghai, China. We are also grateful to all colleagues, who were involved in this study.
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Drexel University
- Web of Science ID
- WOS:000895782700002
- Scopus ID
- 2-s2.0-85143168354
- Other Identifier
- 991021861185004721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Pharmacology & Pharmacy