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  • Title: Divergent phenotypes of vision and accessory visual function in mice with visual cycle dysfunction (Rpe65 rd12) or retinal degeneration (rd/rd).
    Author: Thompson S, Mullins RF, Philp AR, Stone EM, Mrosovsky N.
    Journal: Invest Ophthalmol Vis Sci; 2008 Jun; 49(6):2737-42. PubMed ID: 18515598.
    Abstract:
    PURPOSE: Tests of vision for mice remain limited and the visual phenotype of some retinal disorders in mice remain poorly understood. A novel assay of vision was used to determine how the form and extent of retinal disease affects visual phenotype in mice. METHODS: Retinal histology, the suppression of locomotion by light and visual guidance of locomotion, were assessed in mice with progressive photoreceptor degeneration (rd/rd) or visual cycle dysfunction (Rpe65 rd12). RESULTS: In wild-type mice, there was visual guidance of locomotor activity in dim light and suppression of activity (negative masking) in bright light. In rd/rd mice, vision was sufficient to guide locomotion at postnatal day (P)34 but was lost from P46 onward. In bright light rd/rd mice had enhanced negative masking. Although Rpe65 rd12 mice had no dim light response, with high illumination, vision was sufficient to guide locomotion at all ages tested. CONCLUSIONS: A major concern for gene and cell replacement therapies is the development of visual pathways through which restored retinal function can connect to visual centers of the brain. The residual retinal response to high illumination in Rpe65 rd12 mice translates into useful vision, and visual pathways remain functional--a prerequisite for restoring vision in disorders of the retina. Similarly, useful vision in young rd/rd mice shows that there is visual pathway function before photoreceptor degeneration and suggests the potential for early therapy. Together, these findings recommend observation of masking responses in the assessment of gene and cell replacement therapies.
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