title: Retinal Caveolin-1 Modulates Neuroprotective Signaling.
abstract: Caveolin-1 (Cav-1), the scaffolding protein of caveolae, is expressed in several retinal cell types and is associated with ocular pathologies. Cav-1 modulates neuroinflammatory/neuroprotective responses to central nervous system injury. We have shown that loss of Cav-1 results in a blunted cytokine response in retinas challenged with inflammatory stimuli. As neuroinflammatory and neuroprotective signaling overlap in their cytokine production and downstream signaling pathways, we hypothesized that loss of Cav-1 may also suppress neuroprotective signaling in the retina. To test this, we subjected mice in which Cav-1 was deleted specifically in the retina to a neurodegenerative insult induced by sodium iodate (NaIO3) and measured STAT3 activation, a measure of neuroprotective signaling. Our results show that Cav-1 ablation blunts STAT3 activation induced by NaIO3. STAT3 activation in response to intravitreal administration of the IL-6 family cytokine, leukemia inhibitory factor (LIF), was not affected by Cav-1 deletion indicating a competent gp130 receptor response. Thus, Cav-1 modulates neuroprotective signaling by regulating the endogenous production of neuroprotective factors.
authors.affiliation: Department of Ophthalmology, University of Oklahoma Health Sciences Center, 73104, Oklahoma City, OK, USA. alaina-reagan@ouhsc.edu.|Oklahoma Center for Neuroscience, University of Oklahoma Health Sciences Center, 73104, Oklahoma City, OK, USA. alaina-reagan@ouhsc.edu.|Department of Physiology, University of Oklahoma Health Sciences Center, 73104, Oklahoma City, OK, USA. alaina-reagan@ouhsc.edu.
authors.forename: Alaina
authors.initials: A
authors.lastname: Reagan
authors.affiliation: Department of Ophthalmology, University of Oklahoma Health Sciences Center, 73104, Oklahoma City, OK, USA. xiaowu-gu@ouhsc.edu.|Oklahoma Center for Neuroscience, University of Oklahoma Health Sciences Center, 73104, Oklahoma City, OK, USA. xiaowu-gu@ouhsc.edu.|Department of Physiology, University of Oklahoma Health Sciences Center, 73104, Oklahoma City, OK, USA. xiaowu-gu@ouhsc.edu.
authors.forename: Xiaowu
authors.initials: X
authors.lastname: Gu
authors.affiliation: Research Unit Protein Science, Helmoltz Zentrum München, 85764, Neuherberg, Germany. hauck@helmholtz-muenchen.de.
authors.forename: Stefanie M
authors.initials: SM
authors.lastname: Hauck
authors.affiliation: Department of Ophthalmology Research, University of Florida, 32610, Gainesville, FL, USA. jash@ufl.edu.
authors.forename: John D
authors.initials: JD
authors.lastname: Ash
authors.affiliation: Department of Epidemiology, Second Military Medical University, 200433, Shanghai, China. gcao@smmu.edu.cn.
authors.forename: Guangwen
authors.initials: G
authors.lastname: Cao
authors.affiliation: Department of Genitourinary Medical Oncology-Research, MD Anderson Cancer Center, The University of Texas, 77030, Houston, TX, USA. timthomp@mdanderson.org.
authors.forename: Timothy C
authors.initials: TC
authors.lastname: Thompson
authors.affiliation: Department of Ophthalmology, University of Oklahoma Health Sciences Center, 73104, Oklahoma City, OK, USA. Michael-Elliott@ouhsc.edu.|Oklahoma Center for Neuroscience, University of Oklahoma Health Sciences Center, 73104, Oklahoma City, OK, USA. Michael-Elliott@ouhsc.edu.|Dean A. McGee Eye Institute, University of Oklahoma Health Sciences Center, 608 Stanton L. Young Boulevard Rm. 423, 73104, Oklahoma City, OK, USA. Michael-Elliott@ouhsc.edu.|Department of Physiology, University of Oklahoma Health Sciences Center, 73104, Oklahoma City, OK, USA. Michael-Elliott@ouhsc.edu.
authors.forename: Michael H
authors.initials: MH
authors.lastname: Elliott
mesh_terms: D000818:Animals; D015153:Blotting, Western; D051242:Caveolin 1 / Q000172:deficiency / Q000235:genetics*; D005260:Female; D007150:Immunohistochemistry; D007274:Injections, Intraperitoneal; D007452:Iodates / Q000008:administration & dosage / Q000494:pharmacology; D053605:Leukemia Inhibitory Factor / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D000066829:Neuroprotection / Q000187:drug effects / Q000235:genetics*; D012160:Retina / Q000187:drug effects / Q000378:metabolism*; D055213:Retinal Pigment Epithelium / Q000187:drug effects / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics*
chemical_list: D051242:Caveolin 1; D007452:Iodates; D053605:Leukemia Inhibitory Factor; D050796:STAT3 Transcription Factor; C032285:sodium iodate
keywords: Caveolin-1; Conditional knockout; Cre/lox; Cytokines; Neuroprotection; STAT3; Sodium Iodate