Rpe65 is necessary for production of 11-cis-vitamin A in the retinal visual cycle

S Yu, E Lee, D Bok, D Hamasaki, N Chen, P Goletz… - Nature …, 1998 - nature.com
S Yu, E Lee, D Bok, D Hamasaki, N Chen, P Goletz, JX Ma, RK Crouch, K Pfeifer
Nature genetics, 1998nature.com
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 …
Abstract
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.
nature.com