title: Increased expression of the proton-sensing G protein-coupled receptor Gpr65 during retinal degeneration.
abstract: The retina is a metabolically highly active tissue that is sensitive to pH changes. Blinding diseases of the retina are often characterized by degeneration of photoreceptor cells altering the acid-base homeostasis of the tissue microenvironment and by an accompanying inflammatory response. GPR4, GPR65 and GPR68 are G protein-coupled receptors that aid cells to sense and survive conditions of acidic pH and inflammatory cells express Gpr65 enhancing their viability. Hence, we investigated expression and function of these proton-sensing GPRs in the normal and degenerating retina. We observed increased retinal expression of Gpr65, but not of Gpr4 and Gpr68, in mouse models of both inherited (rd10) and induced (light damage) retinal degeneration. Lack of GPR65 slightly accelerated photoreceptor degeneration in rd10 mice and resulted in a strong activation of microglia after light-injury. Since GPR65 was dispensable for normal retinal development, function and aging as evidenced by the evaluation of Gpr65(-/-) mice, our results indicate that the proton-sensing G protein-coupled receptor GPR65 may be involved in a mechanism that supports survival of photoreceptors in the degenerating retina.
authors.affiliation: Lab for Retinal Cell Biology, Department of Ophthalmology, University of Zürich, Zürich, Switzerland; Neuroscience Center (ZNZ), University of Zürich, Zürich 8057, Switzerland.
authors.forename: D
authors.initials: D
authors.lastname: Ail
authors.affiliation: Lab for Retinal Cell Biology, Department of Ophthalmology, University of Zürich, Zürich, Switzerland.
authors.forename: V
authors.initials: V
authors.lastname: Rüfenacht
authors.affiliation: Lab for Retinal Cell Biology, Department of Ophthalmology, University of Zürich, Zürich, Switzerland.
authors.forename: C
authors.initials: C
authors.lastname: Caprara
authors.affiliation: Lab for Retinal Cell Biology, Department of Ophthalmology, University of Zürich, Zürich, Switzerland.
authors.forename: M
authors.initials: M
authors.lastname: Samardzija
authors.affiliation: Lab for Retinal Cell Biology, Department of Ophthalmology, University of Zürich, Zürich, Switzerland.
authors.forename: B
authors.initials: B
authors.lastname: Kast
authors.affiliation: Lab for Retinal Cell Biology, Department of Ophthalmology, University of Zürich, Zürich, Switzerland; Neuroscience Center (ZNZ), University of Zürich, Zürich 8057, Switzerland; Center for Integrative Human Physiology (ZIHP), University of Zürich, Zürich, Switzerland. Electronic address: cgrimm@opht.uzh.ch.
authors.forename: C
authors.initials: C
authors.lastname: Grimm
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004596:Electroretinography; D005136:Eye Proteins / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000235:genetics*; D008027:Light / Q000009:adverse effects; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism; D012160:Retina / Q000378:metabolism / Q000473:pathology; D012162:Retinal Degeneration / Q000209:etiology / Q000235:genetics* / Q000503:physiopathology*
chemical_list: D016207:Cytokines; D005136:Eye Proteins; C513337:GPR65 protein, mouse; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D043562:Receptors, G-Protein-Coupled
keywords: Gpr65; TDAG8; light damage; microglia; rd10; retinal degeneration