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Akiko Maeda, Tadao Maeda, Krzysztof Palczewski; Improvement in Rod and Cone Function in Mouse Model of Fundus albipunctatus after Pharmacologic Treatment with 9-cis-Retinal. Invest. Ophthalmol. Vis. Sci. 2006;47(10):4540-4546. doi: https://doi.org/10.1167/iovs.06-0215.
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purpose. To assess changes in rod and cone visual functions in a mouse model of Fundus albipunctatus with disrupted 11-cis-retinol dehydrogenase (RDH) genes after pharmacologic treatment with an artificial retinal chromophore.
methods. Retinoid levels and photoreceptor functions of Rdh5 –/– Rdh11 –/– mice at a variety of light intensities were analyzed with normal-phase HPLC and ERG techniques. Production of 11-cis-retinal, the visual pigment chromophore, was suppressed with a potent inhibitor of the retinoid cycle, all-trans-retinylamine (Ret-NH2). The chromophore was replaced by a functional geometric isomer, 9-cis-retinal, delivered by oral gavage.
results. Aberrant cone responses were detected in 12-month-old Rdh5 –/– Rdh11 –/– mice raised in a 12-hour light/12-hour dark cycle. This cone defect was exacerbated in conditions of low levels of 11-cis-retinal. Administration of 9-cis-retinal increased the rate of dark adaptation and improved cone function in Rdh5 –/– Rdh11 –/– mice.
conclusions. Disruption of 11-cis-RDHs causes a slowly developing cone dystrophy caused by inefficient cone pigment regeneration. Rod and cone visual function improved significantly in the mouse model of F. albipunctatus after treatment with 9-cis-retinal, suggesting a potential approach to slow the progression of cone dystrophy in affected humans.
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