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From the Department of Pharmacology, School of Medicine, Case Western Reserve University, Cleveland, Ohio.
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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A. Maeda, T. Maeda, M. Golczak, and K. Palczewski Retinopathy in Mice Induced by Disrupted All-trans-retinal Clearance J. Biol. Chem., September 26, 2008; 283(39): 26684 - 26693. [Abstract] [Full Text] [PDF] |
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