Improvement in Rod and Cone Function in Mouse Model ofFundus albipunctatusafter Pharmacologic Treatment with 9-cis-Retinal
Copyright policy )Improvement in Rod and Cone Function in Mouse Model ofFundus albipunctatusafter Pharmacologic Treatment with 9-cis-Retinal
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.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.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.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.
- Case Western Reserve University United States
Mice, Knockout, Retinal Degeneration, Retinal Dehydrogenase, Dark Adaptation, Disease Models, Animal, Mice, Retinoids, Isomerism, Electroretinography, Retinaldehyde, Animals, Diterpenes, Oxidoreductases, Pigment Epithelium of Eye, Chromatography, High Pressure Liquid, Photoreceptor Cells, Vertebrate
Mice, Knockout, Retinal Degeneration, Retinal Dehydrogenase, Dark Adaptation, Disease Models, Animal, Mice, Retinoids, Isomerism, Electroretinography, Retinaldehyde, Animals, Diterpenes, Oxidoreductases, Pigment Epithelium of Eye, Chromatography, High Pressure Liquid, Photoreceptor Cells, Vertebrate
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