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A. M. Komaromy, J. S. Rowlan, S. L. Reinstein, G. M. Acland, G. D. Aguirre; Gene Expression and Retinal Function in the Developing CNGB3-Achromatopsic Retina. Invest. Ophthalmol. Vis. Sci. 2010;51(13):2585.
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To measure cone- and rod-mediated retinal function and correlate results to cell-specific protein localization during retinal development in 2 canine strains with CNGB3-achromatopsia.
Dogs with either a genomic deletion ("null") or a D262N missense mutation of CNGB3 were studied during and after retinal development. Sequential full-field ERGs were recorded in young dogs from 3 weeks until 2 years of age. Protein expression and localization were analyzed in the same age groups by immunohistochemistry, using cell-type specific antibodies for cones (CNGA3, hCAR, GNAT2, GNB3, L/M- and S-opsin), rods (rhodopsin), and bipolar cells (G0alpha, GNB3), as well as the synaptic markers PSD95 and synaptophysin. All the parameters were compared with age-matched normal controls.
In mutants, cone outer segment elongation during development parallels cone function peak amplitudes at 4 weeks of age. At this time, cone transducins are expressed normally, and small amounts of CNGA3 subunits are present in the outer segments. Cone function is severely depressed by 6 weeks of age, and absent with conventional electroretinography by 8 weeks. At this time, neither cone transducins nor CNGA3 are detectable in the cone outer segments. Other proteins, including the cone opsins and cone arrestin are normally expressed and distributed within the cones both during early development, and after cone function loss. Rod, bipolar cell, and synaptic markers remain unchanged. Our findings are identical for both the CNGB3-null and -missense mutant retinas.
Transient cone function is present as outer segments develop in CNGB3-achromatopsia. This function appears to be mediated by cyclic nucleotide-gated channels made up of CNGA3-subunits. Despite the early and complete loss of function, the morphologic development of the cones is normal.
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