title: Loss of caveolin-1 impairs retinal function due to disturbance of subretinal microenvironment.
abstract: Caveolin-1 (Cav-1), an integral component of caveolar membrane domains, is expressed in several retinal cell types, including photoreceptors, retinal vascular endothelial cells, Müller glia, and retinal pigment epithelium (RPE) cells. Recent evidence links Cav-1 to ocular diseases, including autoimmune uveitis, diabetic retinopathy, and primary open angle glaucoma, but its role in normal vision is largely undetermined. In this report, we show that ablation of Cav-1 results in reduced inner and outer retinal function as measured, in vivo, by electroretinography and manganese-enhanced MRI. Somewhat surprisingly, dark current and light sensitivity were normal in individual rods (recorded with suction electrode methods) from Cav-1 knock-out (KO) mice. Although photoreceptor function was largely normal, in vitro, the apparent K(+) affinity of the RPE-expressed α1-Na(+)/K(+)-ATPase was decreased in Cav-1 KO mice. Cav-1 KO retinas also displayed unusually tight adhesion with the RPE, which could be resolved by brief treatment with hyperosmotic medium, suggesting alterations in outer retinal fluid homeostasis. Collectively, these findings demonstrate that reduced retinal function resulting from Cav-1 ablation is not photoreceptor-intrinsic but rather involves impaired subretinal and/or RPE ion/fluid homeostasis.
authors.affiliation: Department of Ophthalmology and Dean McGee Eye Institute, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73104, USA.
authors.forename: Xiaoman
authors.initials: X
authors.lastname: Li
authors.forename: Mark E
authors.initials: ME
authors.lastname: McClellan
authors.forename: Masaki
authors.initials: M
authors.lastname: Tanito
authors.forename: Philippe
authors.initials: P
authors.lastname: Garteiser
authors.forename: Rheal
authors.initials: R
authors.lastname: Towner
authors.forename: David
authors.initials: D
authors.lastname: Bissig
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Berkowitz
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Fliesler
authors.forename: Michael L
authors.initials: ML
authors.lastname: Woodruff
authors.forename: Gordon L
authors.initials: GL
authors.lastname: Fain
authors.forename: David G
authors.initials: DG
authors.lastname: Birch
authors.forename: M Suhaib
authors.initials: MS
authors.lastname: Khan
authors.forename: John D
authors.initials: JD
authors.lastname: Ash
authors.forename: Michael H
authors.initials: MH
authors.lastname: Elliott
mesh_terms: D000818:Animals; D051242:Caveolin 1 / Q000235:genetics / Q000378:metabolism*; D060833:Cellular Microenvironment / Q000502:physiology*; D006706:Homeostasis / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D020419:Photoreceptor Cells, Vertebrate / Q000166:cytology / Q000378:metabolism*; D011188:Potassium / Q000378:metabolism; D012164:Retinal Diseases / Q000235:genetics / Q000378:metabolism; D055213:Retinal Pigment Epithelium / Q000166:cytology / Q000378:metabolism*; D000254:Sodium-Potassium-Exchanging ATPase / Q000235:genetics / Q000378:metabolism*; D019108:Tight Junctions / Q000235:genetics / Q000378:metabolism*
chemical_list: C495541:Cav1 protein, mouse; D051242:Caveolin 1; C497344:Atp1a1 protein, mouse; D000254:Sodium-Potassium-Exchanging ATPase; D011188:Potassium