title: Improvement in rod and cone function in mouse model of Fundus albipunctatus after pharmacologic treatment with 9-cis-retinal.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Pharmacology, School of Medicine, Case Western Reserve University, Cleveland, Ohio 44106-4965, USA. aam19@case.edu
authors.forename: Akiko
authors.initials: A
authors.lastname: Maeda
authors.forename: Tadao
authors.initials: T
authors.lastname: Maeda
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Palczewski
mesh_terms: D000818:Animals; D002851:Chromatography, High Pressure Liquid; D003623:Dark Adaptation; D004195:Disease Models, Animal; D004224:Diterpenes; D004596:Electroretinography; D007536:Isomerism; D051379:Mice; D018345:Mice, Knockout; D010088:Oxidoreductases / Q000502:physiology; D020419:Photoreceptor Cells, Vertebrate / Q000502:physiology*; D010857:Pigment Epithelium of Eye / Q000502:physiology; D012162:Retinal Degeneration / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D050697:Retinal Dehydrogenase / Q000502:physiology; D012172:Retinaldehyde / Q000627:therapeutic use*; D012176:Retinoids / Q000378:metabolism
chemical_list: D004224:Diterpenes; D012176:Retinoids; C031390:9-cis-retinal; D010088:Oxidoreductases; C486028:Rdh11 protein, mouse; D050697:Retinal Dehydrogenase; D012172:Retinaldehyde