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S.E. Haire, J. Pang, S. Boye, A. Robinson, I. Sokal, C. Craft, K. Palczewski, W.W. Hauswirth, S.L. Semple–Rowland; AAV–GC1 Restores Subcellular Distribution of Cone Arrestin and GCAP1 Expression in Cone Cells of the GC1 Ko Mouse . Invest. Ophthalmol. Vis. Sci. 2006;47(13):838.
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We have shown that the absence of guanylate cyclase–1 (GC1) in the GC1 knockout mouse prevents normal, light–driven translocation of cone arrestin in cone cells. In these retinas, cone arrestin immunoreactivity is localized to the outer segments and synaptic terminals of cone cells regardless of the state of light adaptation. In addition, levels of guanylate cyclase activating protein–1 (GCAP1) are downregulated in cone cells of the GC1 KO mouse prior to the onset of cone cell degeneration. The purpose of this study was to examine the effects of AAV delivered GC1 on the distribution of arrestin and GCAP1 expression in GC1 KO cone photoreceptors.
Three–week–old GC1 KO mice received subretinal injections of AAV–GC1 and their retinas were examined 5 weeks post–injection. Immunohistochemical techniques employing GC1 (IS4 – I. Sokal), cone arrestin (LUMIj –Zhu & Craft) and cone transducin alpha (UW14– K. Palczewski) antibodies were used to identify photoreceptors transduced by the AAV vector and to localize cone arrestin and GCAP1, respectively.
In dark–adapted, GC1 KO retinas treated with AAV–GC1, cone arrestin was distributed throughout the transduced cells, the staining pattern resembling that observed in dark–adapted, wild–type retinas. AAV–GC1 treated cone cells had increased levels of GCAP1 expression as compared to GC1 KO cone photoreceptors.
AAV– mediated delivery of GC1 to cone photoreceptors in the GC1 KO mouse retina restores the normal sub–cellular distribution of cone arrestin and increases levels of GCAP1 protein in these cells. These results confirm that light–driven translocation of arrestin and GCAP1 expression in cone cells is dependent on expression of GC1 in these cells.
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