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Jianhua Xu, Lynsie Morris, Steven J. Fliesler, David M. Sherry, Xi-Qin Ding; Early-Onset, Slow Progression of Cone Photoreceptor Dysfunction and Degeneration in CNG Channel Subunit CNGB3 Deficiency. Invest. Ophthalmol. Vis. Sci. 2011;52(6):3557-3566. doi: https://doi.org/10.1167/iovs.10-6358.
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© ARVO (1962-2015); The Authors (2016-present)
To investigate the progression of cone dysfunction and degeneration in CNG channel subunit CNGB3 deficiency.
Retinal structure and function in CNGB3−/− and wild-type (WT) mice were evaluated by electroretinography (ERG), lectin cytochemistry, and correlative Western blot analysis of cone-specific proteins. Cone and rod terminal integrity was assessed by electron microscopy and synaptic protein immunohistochemical distribution.
Cone ERG amplitudes (photopic b-wave) in CNGB3−/− mice were reduced to approximately 50% of WT levels by postnatal day 15, decreasing further to approximately 30% of WT levels by 1 month and to approximately 20% by 12 months of age. Rod ERG responses (scotopic a-wave) were not affected in CNGB3−/− mice. Average CNGB3−/− cone densities were approximately 80% of WT levels at 1 month and declined slowly thereafter to only approximately 50% of WT levels by 12 months. Expression levels of M-opsin, cone transducin α-subunit, and cone arrestin in CNGB3−/− mice were reduced by 50% to 60% by 1 month and declined to 35% to 45% of WT levels by 9 months. In addition, cone opsin mislocalized to the outer nuclear layer and the outer plexiform layer in the CNGB3−/− retina. Cone and rod synaptic marker expression and terminal ultrastructure were normal in the CNGB3−/− retina.
These findings are consistent with an early-onset, slow progression of cone functional defects and cone loss in CNGB3−/− mice, with the cone signaling deficits arising from disrupted phototransduction and cone loss rather than from synaptic defects.
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