期刊
NEUROBIOLOGY OF AGING
卷 36, 期 6, 页码 2201-2212出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.neurobiolaging.2015.02.012
关键词
POAG; Neurodegeneration; Optineurin; Retinal ganglion cells; Mouse model; Vision
资金
- American Glaucoma Society
- Butler Pioneer Award
- Howard Hughes Medical Institute
- NEI core grant [P30-EY005722]
- [K12-EY016333]
- [K08-EY021520]
- [R01-EY11721]
- [R01-EY018323]
- Div Of Biological Infrastructure
- Direct For Biological Sciences [1262049] Funding Source: National Science Foundation
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. (C) 2015 Elsevier Inc. All rights reserved.
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