Analysis of the visual cycle in cellular retinol-binding protein type I (CRBPI) knockout mice.
OBJECTIVE
To determine whether the visual cycle is affected in mice without a functional gene for cellular retinol-binding protein type I (CRBPI(-/-) mice).


METHODS
Visual-cycle retinoids and rhodopsin levels were analyzed in eyes of dark adapted (DA) CRBPI(-/-) and wild-type (wt) mice before and during recovery from a flash. The rate of dark adaptation was analyzed using electroretinography (ERG).


RESULTS
all-trans-retinyl esters were reduced to approximately 33% of wt levels in DA CRBPI(-/-) mice. Recovery from a flash in wt mice produced transient accumulations of all-trans-retinal and all-trans-retinyl ester, as the pulse of retinoid produced by the flash traversed the visual cycle. In CRBPI(-/-) mice, all-trans-retinal accumulated transiently, as in wt mice. However, all-trans-retinol also accumulated transiently in the neural retina, and the transient increase in all-trans-retinyl ester of the wt was reduced. Rates of 11-cis-retinal and rhodopsin formation were comparable in wt and CRBPI(-/-) mice. Dark adaptation was delayed by a factor of approximately two.


CONCLUSIONS
The accumulation of all-trans-retinol in neural retina, in the absence of CRBPI and the reduced amount of retinyl esters in the RPE suggest that the binding protein participates in a process that drives diffusion of all-trans-retinol from photoreceptor cells to RPE, perhaps by delivering vitamin A to lecithin-retinol acyltransferase (LRAT) for esterification. Because the perturbation occurred upstream of a slow step of the visual cycle, there was no major impairment of the rate of visual pigment regeneration.
Saari
John C
JC
Departments of Ophthalmology, University of Washington, Seattle, Washington 98195-6485, USA. jsaari@u.washington.edu
Nawrot
Maria
M
Garwin
Gregory G
GG
Kennedy
Matthew J
MJ
Hurley
James B
JB
Ghyselinck
Norbert B
NB
Chambon
Pierre
P
D000217:Acyltransferases / Q000378:metabolism; D000818:Animals; D002453:Cell Cycle / Q000502:physiology; D003623:Dark Adaptation; D004596:Electroretinography; D051379:Mice; D018345:Mice, Knockout; D010775:Photic Stimulation; D012160:Retina / Q000166:cytology / Q000378:metabolism*; D012176:Retinoids / Q000378:metabolism*; D012177:Retinol-Binding Proteins / Q000502:physiology*; D054840:Retinol-Binding Proteins, Cellular; D012243:Rhodopsin / Q000378:metabolism*; D014785:Vision, Ocular / Q000502:physiology*; D014801:Vitamin A / Q000378:metabolism
D012176:Retinoids; D012177:Retinol-Binding Proteins; D054840:Retinol-Binding Proteins, Cellular; D014801:Vitamin A; D012243:Rhodopsin; D000217:Acyltransferases; C056942:lecithin-retinol acyltransferase