Visual impairment in an optineurin mouse model of primary open-angle glaucoma
HC Tseng, TT Riday, C McKee, CE Braine… - Neurobiology of …, 2015 - Elsevier
HC Tseng, TT Riday, C McKee, CE Braine, H Bomze, I Barak, C Marean-Reardon…
Neurobiology of aging, 2015•ElsevierPrimary 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 …
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 …
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.
Elsevier
