期刊
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
卷 53, 期 3, 页码 1117-1129出版社
ASSOC RESEARCH VISION OPHTHALMOLOGY INC
DOI: 10.1167/iovs.11-8168
关键词
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资金
- NCRR [P20 RR017703]
- NIH/NEI [P30 EY12190, R01 EY019490, R01 EY007361]
- American Health Assistance Foundation
- Oklahoma Center for the Advancement of Science & Technology (OCAST)
- Deutsche Forschungsgemeinschaft (DFG)
- Research to Prevent Blindness
PURPOSE. To investigate rod function and survival after cone dysfunction and degeneration in a mouse model of cone cyclic nucleotide-gated (CNG) channel deficiency. METHODS. Rod function and survival in mice with cone CNG channel subunit CNGA3 deficiency (CNGA3(-/-) mice) were evaluated by electroretinographic (ERG), morphometric, and Western blot analyses. The arrangement, integrity, and ultrastructure of photoreceptor terminals were investigated by immunohistochemistry and electron microscopy. RESULTS. The authors found loss of cone function and cone death accompanied by impairment of rods and rod-driven signaling in CNGA3(-/-) mice. Scotopic ERG b-wave amplitudes were reduced by 15% at 1 month, 30% at 6 months, and 40% at 9 months and older, while scotopic a-wave amplitudes were decreased by 20% at 9 months, compared with ERGs of age-matched wild-type mice. Outer nuclear layer thickness in CNGA3(-/-) retina was reduced by 15% at 12 months compared with age-matched wild-type controls. This was accompanied by a 30%-40% reduction in expression of rod-specific proteins, including rhodopsin, rod transducin alpha-subunit, and glutamic acid-rich protein (GARP). Cone terminals in the CNGA3(-/-) retina showed a progressive loss of neurochemical and ultrastructural integrity. Abnormalities were observed as early as 1 month. Disorganized rod terminal ultrastructure was noted by 12 months. CONCLUSIONS. These findings demonstrate secondary rod impairment and degeneration after cone degeneration in mice with cone CNG channel deficiency. Loss of cone phototransduction accompanies the compromised integrity of cone terminals. With time, rod synaptic structure, function, and viability also become compromised. (Invest Ophthalmol Vis Sci. 2012;53:1117-1129) DOI:10.1167/iovs.11-8168
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