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C. Bonetti, C. Mussolino, U. Di Vicino, D. O'Leary, L. Dominici, E. Surace; Reduction of Thalamocortical Projections in Ocular Albinism Type I Mouse Model Impacts on Visual Cortex Maturation. Invest. Ophthalmol. Vis. Sci. 2008;49(13):3867. doi: https://doi.org/.
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Ocular Albinism type I (OA1) is an X-linked recessive disease due to mutations in the OA1 gene, which is expressed in melanocytes and retinal pigment epithelium (RPE). The OA1 patients show visual abnormalities common to all forms of albinism including foveal hypoplasia that causes reduction in visual acuity, nystagmus and misrouting of optic fibers at the chiasm. In this work, we characterize the visual system of Oa1-/- mice from the eye to the visual cortex and how the lack of OA1 impacts on visual cortex connectivity and plasticity.
Electron microscopy was used to determine the number of Retinal Ganglion Cells (RGCs) at the level of optic nerve in Oa1-/- mice. dLGN volumes of ipsi and contra-lateral components was performed by intra-ocular injection of Cholera-Toxin. To characterize thalamo-cortical projections (TCA) we used DiI labeling injection in dLGN and a genetic labeling approach by crossing Oa1-/- animals with Rorα-Cre/Rosa26 transgenic mice (expressing YFP specifically in the TCA). In situ hybridization (ISH) and Real Time PCR were done to study expression pattern of molecules implicated in cortical connectivity and plasticity such as of neurotrophins (BDNF), Immediately Early genes (c-Fos, Arc) and genes involved in GABAergic circuit maturation (Parvalbumin KCC2, GABA A receptors, CamKII) during and after the Critical Period (from P17 to P34 and in adult). Visual cortex plasticy is being assessed during the critical period by Arc ISH after 4 days of monocular deprivation.
We found a 30% reduction of RGCs axons in Oa1-/- mice. This was consistent with an overall reduction of total volume of dLGN: specifically the ipsi-lateral component was 30% reduced whereas we observed a 15% reduction in the contra-lateral component. Immunohistochemistry analysis on Oa1-/-/Rorα-Cre/Rosa26 transgenic mice revealed a reduction of 30% of YFP positive TCA. Interestingly the expression profile of molecules implicated in visual cortex refinement and plasticity were altered.
Oa1 null mutation affects the entire visual pathway from the eye to the cortex. In particular, the reduction of TCA projections impacts on visual cortical maturation, suggesting novel insights into molecular bases of albinism.
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