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A. Hussain Batcha, J. Nithianantharajah, A. Hannan, E. Fletcher; Photoreceptor Dysfunction in Transgenic Huntington’s Disease Mice. Invest. Ophthalmol. Vis. Sci. 2008;49(13):3006. doi: https://doi.org/.
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Huntington’s disease(HD) is a fatal neurodegenerative disorder caused by a mutation in the huntingtin gene. Altered visual function has been reported, although not well characterized. The aim of this study was to examine in detail retinal structure and function in a R6/1 transgenic mouse model of HD at a stage prior to the development of advance motor deficits.
Retinal function of wild-type mice (WT; N=9) and R6/1 HD mice (N=11) at 13-14 weeks of age was measured using a twin flash electroretinogram paradigm. Following measurements of retinal function, all eyes were dissected and fixed in either 4% paraformaldehyde for 30 minutes or overnight in a fixative containing glutaraldehyde/paraformaldehyde. Tissues were processed for indirect immunofluorescence/resin embedded. Thickness of retinal layers was measured in Toluedene blue stained sections. Presence of rods and cones was determined by immunolabelling with antibodies directed against rhodopsin, S-cone opsin, L/M-cone opsin and peanut agluttinin(PNA). Tissues of 7 weeks old R6/1 HD mice (N=5) and WT mice (N=5) were also collected and processed as mentioned above. The presence of apoptosis was determined by TUNEL labeling and single-stranded DNA.
Electrophysiological findings revealed reduced cone and variable rod responses in HD mice. The thickness of retinae at 13-14 weeks as well as 7 weeks was similar in both HD and WT mice. Immunolabelling for cone opsins, but not PNA was significantly reduced in HD mice at 13-14 weeks, suggesting a defect in the expression of cone opsins whereas there was no change in the number of cones labeled with cone opsins and PNA at 7 weeks of age. In addition there was widespread apoptosis in the outer nuclear layer.
We conclude that retinal function in R6/1 Huntington’s disease mice is associated with significant functional loss of photoreceptors, especially cones. Further work is necessary to determine the influence of these findings on cognition and behaviour in this mouse model and its significance in human disease.
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