title: Visual impairment in an optineurin mouse model of primary open-angle glaucoma.
abstract: Primary open-angle glaucoma (POAG) is characterized by progressive neurodegeneration of retinal ganglion cells (RGCs). Why RGCs degenerate in low-pressure POAG remains poorly understood. To gain mechanistic insights, we developed a novel mouse model based on a mutation in human optineurin associated with hereditary, low-pressure POAG. This mouse improves the design and phenotype of currently available optineurin mice, which showed high global overexpression. Although both 18-month-old optineurin and nontransgenic control mice showed an age-related decrease in healthy axons and RGCs, the expression of mutant optineurin enhanced axonal degeneration and decreased RGC survival. Mouse visual function was determined using visual evoked potentials, which revealed specific visual impairment in contrast sensitivity. The E50K optineurin transgenic mouse described here exhibited clinical features of POAG and may be useful for mechanistic dissection of POAG and therapeutic development.
authors.affiliation: Duke Eye Center, Department of Ophthalmology, Duke University Medical Center, Durham, NC, USA. Electronic address: Henry.Tseng@duke.edu.
authors.forename: Henry C
authors.initials: HC
authors.lastname: Tseng
authors.affiliation: Department of Cell Biology and Physiology, Neuroscience Center, Carolina Institute for Developmental Disabilities, University of North Carolina School of Medicine, Chapel Hill, NC, USA.
authors.forename: Thorfinn T
authors.initials: TT
authors.lastname: Riday
authors.affiliation: Duke Eye Center, Department of Ophthalmology, Duke University Medical Center, Durham, NC, USA.
authors.forename: Celia
authors.initials: C
authors.lastname: McKee
authors.affiliation: The Jackson Laboratory, Bar Harbor, ME, USA.
authors.forename: Catherine E
authors.initials: CE
authors.lastname: Braine
authors.affiliation: Duke Eye Center, Department of Ophthalmology, Duke University Medical Center, Durham, NC, USA.
authors.forename: Howard
authors.initials: H
authors.lastname: Bomze
authors.affiliation: Duke Eye Center, Department of Ophthalmology, Duke University Medical Center, Durham, NC, USA.
authors.forename: Ian
authors.initials: I
authors.lastname: Barak
authors.affiliation: Duke Eye Center, Department of Ophthalmology, Duke University Medical Center, Durham, NC, USA.
authors.forename: Carrie
authors.initials: C
authors.lastname: Marean-Reardon
authors.affiliation: The Jackson Laboratory, Bar Harbor, ME, USA; The Howard Hughes Medical Institute, The Jackson Laboratory, Bar Harbor, ME, USA; Department of Ophthalmology, Tufts University School of Medicine, Boston, MA, USA.
authors.forename: Simon W M
authors.initials: SW
authors.lastname: John
authors.affiliation: Department of Cell Biology and Physiology, Neuroscience Center, Carolina Institute for Developmental Disabilities, University of North Carolina School of Medicine, Chapel Hill, NC, USA.
authors.forename: Benjamin D
authors.initials: BD
authors.lastname: Philpot
authors.affiliation: Department of Neurobiology and Howard Hughes Medical Institute, Duke University Medical Center, Durham, NC, USA.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Ehlers
mesh_terms: D000818:Animals; D001369:Axons / Q000473:pathology; D018797:Cell Cycle Proteins; D002470:Cell Survival / Q000235:genetics; D004195:Disease Models, Animal; D005074:Evoked Potentials, Visual; D005136:Eye Proteins / Q000235:genetics*; D005902:Glaucoma, Open-Angle / Q000235:genetics* / Q000473:pathology; D006801:Humans; D026901:Membrane Transport Proteins; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009154:Mutation; D009410:Nerve Degeneration / Q000235:genetics; D012165:Retinal Ganglion Cells / Q000473:pathology; D014786:Vision Disorders / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology
chemical_list: D018797:Cell Cycle Proteins; D005136:Eye Proteins; D026901:Membrane Transport Proteins; C501288:Optn protein, mouse
keywords: Mouse model; Neurodegeneration; Optineurin; POAG; Retinal ganglion cells; Vision
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