Rpe65 is necessary for production of 11-cis-vitamin A in the retinal visual cycle.
Mutation 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.
Redmond
T M
TM
Laboratory of Retinal Cell and Molecular Biology, National Eye Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. redmond@helix.nih.gov
Yu
S
S
Lee
E
E
Bok
D
D
Hamasaki
D
D
Chen
N
N
Goletz
P
P
Ma
J X
JX
Crouch
R K
RK
Pfeifer
K
K
D000818:Animals; D002352:Carrier Proteins; D004952:Esters; D005136:Eye Proteins / Q000235:genetics / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D008854:Microscopy, Electron; D009154:Mutation; D010641:Phenotype; D011506:Proteins; D012160:Retina / Q000502:physiology* / Q000648:ultrastructure; D017948:Retinal Rod Photoreceptor Cells / Q000378:metabolism / Q000502:physiology; D012243:Rhodopsin / Q000378:metabolism; D014785:Vision, Ocular / Q000502:physiology*; D014801:Vitamin A / Q000096:biosynthesis* / Q000378:metabolism; D019745:cis-trans-Isomerases; D000099178:Retinoid Isomerohydrolase
D002352:Carrier Proteins; D004952:Esters; D005136:Eye Proteins; D011506:Proteins; D012243:Rhodopsin; D014801:Vitamin A; D019745:cis-trans-Isomerases; D000099178:Retinoid Isomerohydrolase