Nature Genetics
20, 344 - 351 (1998)
doi:10.1038/3813
Rpe65 is necessary for production of 11-cis-vitamin A in
the retinal visual cycleT. Michael Redmond.1, Shirley Yu1, Eric Lee2, Dean Bok3, Duco Hamasaki4, Ning Chen5, Patrice Goletz5, Jian-Xing Ma5, Rosalie K. Crouch5
& Karl Pfeifer21
Laboratory of Retinal Cell and Molecular Biology, National
Eye Institute, Bethesda, Maryland 20892, USA. 2
Laboratory of Mammalian Genes and Development, National
Institute of Child Health and Human Development, National Institutes of Health,
Bethesda, Maryland 20892, USA. 3
Jules Stein Eye Institute, Brain Research Institute
and Department of Neurobiology, UCLA School of Medicine, Los Angeles,
California 90095, USA. 4
Bascom-Palmer Eye Institute, University of Miami School
of Medicine, Miami, Florida 33101, USA. 5
Storm Eye Institute, Medical University of South Carolina,
Charleston, South Carolina 29425, USA.
Correspondence should be addressed to T. Michael Redmond. redmond@helix.nih.govMutation of RPE65 can cause severe blindness from birth or early
childhood, and RPE65 protein is associated with retinal pigment epithelium
(RPE) vitamin A metabolism. Here, we show that Rpe65-deficient mice
exhibit changes in retinal physiology and biochemistry. Outer segment discs
of rod photoreceptors in Rpe65−/− mice are
disorganized compared with those of Rpe65+/+ and
Rpe65+/− mice. Rod function, as measured by electroretinography,
is abolished in Rpe65−/− mice, although
cone function remains. Rpe65
−/− mice lack
rhodopsin, but not opsin apoprotein. Furthermore, all-trans-retinyl
esters over-accumulate in the RPE of Rpe65−/−
mice, whereas 11-cis-retinyl esters are absent. Disruption of the RPE-based
metabolism of all-trans-retinyl esters to 11-cis-retinal thus
appears to underlie the Rpe65-/- phenotype, although
cone pigment regeneration may be dependent on a separate pathway.
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