Improvement in rod and cone function in mouse model of Fundus albipunctatus after pharmacologic treatment with 9-cis-retinal.

Abstract

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.

• Authors: Akiko Maeda, Tadao Maeda, Krzysztof Palczewski
• Journal: Investigative ophthalmology & visual science (Invest Ophthalmol Vis Sci) Vol. 47 Issue 10 Pg. 4540-6 (Oct 2006) ISSN: 0146-0404 [Print] United States
• PMID: 17003450 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Diterpenes
• Retinoids
• 9-cis-retinal
• Oxidoreductases
• Rdh11 protein, mouse
• Retinal Dehydrogenase
• Retinaldehyde

Topics

• Animals
• Chromatography, High Pressure Liquid
• Dark Adaptation
• Disease Models, Animal
• Diterpenes
• Electroretinography
• Isomerism
• Mice
• Mice, Knockout
• Oxidoreductases (physiology)
• Photoreceptor Cells, Vertebrate (physiology)
• Pigment Epithelium of Eye (physiology)
• Retinal Degeneration (drug therapy, metabolism, physiopathology)
• Retinal Dehydrogenase (physiology)
• Retinaldehyde (therapeutic use)
• Retinoids (metabolism)