title: Conditional Induction of Oxidative Stress in RPE: A Mouse Model of Progressive Retinal Degeneration.
abstract: An appropriate animal model is essential to screening drugs or designing a treatment strategy for geographic atrophy. Since oxidative stress contributes to the pathological changes of the retinal pigment epithelium (RPE), we are reporting a new mouse AMD model of retinal degeneration by inducing mitochondrial oxidative stress in RPE. Sod2 the gene for manganese superoxide dismutase (MnSOD) was deleted in RPE layer using conditional knockout strategy. Fundus microscopy, SD-OCT and electroretinography were used to monitor retinal structure and function in living animals and microscopy was used to assess pathology post mortem. Tissue specific deletion of Sod2 caused elevated signs of oxidative stress, RPE dysfunction and showed some key features of AMD. Due to induction of oxidative stress, the conditional knockout mice show progressive reduction in ERG responses and thinning of outer nuclear layer (ONL) compared to non-induced littermates.
authors.affiliation: Department of Molecular Genetics and Microbiology, College of Medicine, University of Florida, 1200 Newell Drive, 32610-0266, PO Box 100266-MGM, Gainesville, FL, USA. biswal@ufl.edu.
authors.forename: Manas R
authors.initials: MR
authors.lastname: Biswal
authors.affiliation: Department of Molecular Genetics and Microbiology, College of Medicine, University of Florida, 1200 Newell Drive, 32610-0266, PO Box 100266-MGM, Gainesville, FL, USA. ildefons@ufl.edu.
authors.forename: Cristhian J
authors.initials: CJ
authors.lastname: Ildefonso
authors.affiliation: Department of Molecular Genetics and Microbiology, College of Medicine, University of Florida, 1200 Newell Drive, 32610-0266, PO Box 100266-MGM, Gainesville, FL, USA.
authors.forename: Haoyu
authors.initials: H
authors.lastname: Mao
authors.affiliation: Department of Molecular Genetics and Microbiology, College of Medicine, University of Florida, 1200 Newell Drive, 32610-0266, PO Box 100266-MGM, Gainesville, FL, USA.
authors.forename: Soo Jung
authors.initials: SJ
authors.lastname: Seo
authors.affiliation: Department of Molecular Genetics and Microbiology, College of Medicine, University of Florida, 1200 Newell Drive, 32610-0266, PO Box 100266-MGM, Gainesville, FL, USA. zhaokekewzy@hotmail.com.
authors.forename: Zhaoyang
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Molecular Genetics and Microbiology, College of Medicine, University of Florida, 1200 Newell Drive, 32610-0266, PO Box 100266-MGM, Gainesville, FL, USA.
authors.forename: Hong
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Endocrinology and Diabetes, University of Oklahoma Health Science Center, 73104, Oklahoma city, OK, USA. yun-le@ouhsc.edu.
authors.forename: Yun Z
authors.initials: YZ
authors.lastname: Le
authors.affiliation: Department of Molecular Genetics and Microbiology, College of Medicine, University of Florida, 1200 Newell Drive, 32610-0266, PO Box 100266-MGM, Gainesville, FL, USA. lewin@ufl.edu.
authors.forename: Alfred S
authors.initials: AS
authors.lastname: Lewin
mesh_terms: D000818:Animals; D000075002:Bestrophins; D004195:Disease Models, Animal; D004596:Electroretinography; D005136:Eye Proteins / Q000235:genetics; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007473:Ion Channels / Q000235:genetics; D008268:Macular Degeneration / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D019721:Ophthalmoscopes; D009887:Ophthalmoscopy / Q000379:methods; D018384:Oxidative Stress; D012162:Retinal Degeneration / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D055213:Retinal Pigment Epithelium / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D013482:Superoxide Dismutase / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D041623:Tomography, Optical Coherence; D000099156:Superoxide Dismutase 2
chemical_list: D000075002:Bestrophins; D005136:Eye Proteins; D007473:Ion Channels; D013482:Superoxide Dismutase; D000099156:Superoxide Dismutase 2; C491856:Best1 protein, mouse
keywords: Age related macular degeneration; Geographic atrophy; Knockout mice; Oxidative stress; Retinal degeneration; Retinal pigment epithelium; Superoxide dismutase