title: Protection of retina by αB crystallin in sodium iodate induced retinal degeneration.
abstract: Age-related macular degeneration (AMD) is a leading cause of blindness in the developed world. The retinal pigment epithelium (RPE) is a critical site of pathology in AMD and αB crystallin expression is increased in RPE and associated drusen in AMD. The purpose of this study was to investigate the role of αB crystallin in sodium iodate (NaIO3)-induced retinal degeneration, a model of AMD in which the primary site of pathology is the RPE. Dose dependent effects of intravenous NaIO3 (20-70 mg/kg) on development of retinal degeneration (fundus photography) and RPE and retinal neuronal loss (histology) were determined in wild type and αB crystallin knockout mice. Absence of αB crystallin augmented retinal degeneration in low dose (20 mg/kg) NaIO3-treated mice and increased retinal cell apoptosis which was mainly localized to the RPE layer. Generation of reactive oxygen species (ROS) was observed with NaIO3 in mouse and human RPE which increased further after αB crystallin knockout or siRNA knockdown, respectively. NaIO3 upregulated AKT phosphorylation and peroxisome proliferator-activator receptor-γ (PPARγ) which was suppressed after αB crystallin siRNA knockdown. Further, PPARγ ligand inhibited NaIO3-induced ROS generation. Our data suggest that αB crystallin plays a critical role in protection of NaIO3-induced oxidative stress and retinal degeneration in part through upregulation of AKT phosphorylation and PPARγ expression.
authors.affiliation: Doheny Eye Institute, Los Angeles, California, United States of America.
authors.forename: Peng
authors.initials: P
authors.lastname: Zhou
authors.affiliation: Doheny Eye Institute, Los Angeles, California, United States of America.
authors.forename: Ram
authors.initials: R
authors.lastname: Kannan
authors.affiliation: Ophthalmology, Keck School of Medicine of the University of Southern California, Los Angeles, California, United States of America.
authors.forename: Christine
authors.initials: C
authors.lastname: Spee
authors.affiliation: Doheny Eye Institute, Los Angeles, California, United States of America.
authors.forename: Parameswaran G
authors.initials: PG
authors.lastname: Sreekumar
authors.affiliation: Doheny Eye Institute, Los Angeles, California, United States of America.
authors.forename: Guorui
authors.initials: G
authors.lastname: Dou
authors.affiliation: Departments of Pathology, Keck School of Medicine of the University of Southern California, Los Angeles, California, United States of America; Ophthalmology, Keck School of Medicine of the University of Southern California, Los Angeles, California, United States of America.
authors.forename: David R
authors.initials: DR
authors.lastname: Hinton
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D053148:Caspase 3 / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects / Q000235:genetics; D004195:Disease Models, Animal; D004596:Electroretinography; D004789:Enzyme Activation; D055785:Gene Knockdown Techniques; D006801:Humans; D007452:Iodates / Q000009:adverse effects; D008268:Macular Degeneration / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D034622:RNA Interference; D017382:Reactive Oxygen Species / Q000378:metabolism; D012160:Retina / Q000378:metabolism / Q000473:pathology; D012162:Retinal Degeneration / Q000139:chemically induced / Q000235:genetics* / Q000473:pathology*; D055213:Retinal Pigment Epithelium / Q000378:metabolism / Q000473:pathology; D042261:Retinoscopes; D015398:Signal Transduction; D038203:alpha-Crystallin B Chain / Q000235:genetics* / Q000378:metabolism
chemical_list: D007452:Iodates; D017382:Reactive Oxygen Species; D038203:alpha-Crystallin B Chain; D053148:Caspase 3; C032285:sodium iodate