Retinal Detachment-Induced Müller Glial Cell Swelling Activates TRPV4 Ion Channels and Triggers Photoreceptor Death at Body Temperature

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
H MatsumotoKoji Shibasaki

Abstract

Using region-specific injection of hyaluronic acid, we developed a mouse model of acute retinal detachment (RD) to investigate molecular mechanisms of photoreceptor cell death triggered by RD. We focused on the transient receptor potential vanilloid 4 (TRPV4) ion channel, which functions as a thermosensor, osmosensor, and/or mechanosensor. After RD, the number of apoptotic photoreceptors was reduced by ∼50% in TRPV4KO mice relative to wild-type mice, indicating the possible involvement of TRPV4 activation in RD-induced photoreceptor cell death. Furthermore, TRPV4 expressed in Müller glial cells can be activated by mechanical stimuli caused by RD-induced swelling of these cells, resulting in release of the cytokine MCP-1, which is reported as a mediator of Müller glia-derived strong mediator for RD-induced photoreceptor death. We also found that the TRPV4 activation by the Müller glial swelling was potentiated by body temperature. Together, our results suggest that RD adversely impacts photoreceptor viability via TRPV4-dependent cytokine release from Müller glial cells and that TRPV4 is part of a novel molecular pathway that could exacerbate the effects of hypoxia on photoreceptor survival after RD.SIGNIFICANCE STATEMENT Identif...Continue Reading

Citations

Oct 24, 2019·Laboratory Investigation; a Journal of Technical Methods and Pathology·Koji ShibasakiYasuki Ishizaki
Jan 10, 2020·Molecular Neurobiology·Rupali Vohra, Miriam Kolko
Apr 10, 2020·Investigative Ophthalmology & Visual Science·Luka LapajneDavid Križaj
Jan 4, 2020·Laboratory Investigation; a Journal of Technical Methods and Pathology·Koji Shibasaki
Sep 19, 2020·Investigative Ophthalmology & Visual Science·María Llorián-SalvadorHeping Xu
Aug 7, 2019·Journal of Neuroscience Research·Yukie HiraharaHisao Yamada
Dec 18, 2019·Laboratory Investigation; a Journal of Technical Methods and Pathology·Mai OdaKoji Shibasaki
Sep 7, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Qian LiJihong Wu
Oct 28, 2019·Acta Ophthalmologica·Andreas BringmannPeter Wiedemann
Feb 2, 2021·Investigative Ophthalmology & Visual Science·Hong LiShibo Tang
Jan 13, 2021·Brain Research Bulletin·Zi-Yuan ZhangGuang-Yu Li
Feb 19, 2021·Nanoscale·Roberta FabbriValentina Benfenati
Feb 25, 2021·Glia·Sarah N RedmonDavid Križaj
Apr 10, 2020·Progress in Retinal and Eye Research·Marina S GorbatyukOleg S Gorbatyuk
Oct 15, 2020·Science Signaling·Roberta GualdaniPhilippe Gailly
Nov 17, 2020·Experimental Eye Research·Marcela S VeraNora P Rotstein
Jul 30, 2021·Scientific Reports·Harumasa YokotaMasahiko Shimura
Sep 27, 2020·Experimental Eye Research·Brianna D GuarinoCharles K Thodeti

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