Spinocerebellar ataxia type 1 (SCA1) affects not only the cerebellum but also the retina; however, retinal pathology remains poorly characterised in murine models of SCA1. To fill this gap, we performed a comprehensive stereological analysis of the retinal structure of SCA1154Q/2Q knock-in mice and their healthy SCA12Q/2Q littermates at 6 and 10 months of age. We compared animals across genotypes at each age and across ages within each genotype. Using unbiased stereology, we quantified the total retinal volume, volumes of individual retinal layers, total photoreceptor numbers, numbers of rods and cones, and total cell numbers in the inner nuclear and ganglion cell layers. Structural abnormalities, including disorganisation of photoreceptor outer segments and reduced volumes of both photoreceptor inner and outer segments, were evident in SCA1 mice as early as 6 months. By 10 months, these alterations had progressed, with a decrease in the number of ganglion cells and a reduced proportion of cones among the total photoreceptors. Wild-type mice also exhibited age-related changes, but the pattern and magnitude differed, suggesting distinct mechanisms of normal ageing versus SCA1-related neurodegeneration. Our findings demonstrate that retinal remodelling in SCA1 mice parallels changes observed in human patients, validating this model for investigating visual system involvement in SCA1. These results emphasize the need to consider retinal pathology when interpreting behavioural or motor deficits and in designing future preclinical interventions.
Keywords: Mouse model; Retina morphology; Spinocerebellar ataxia type 1; Stereological analysis.
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