Oxyopia Abstract

October 11, 2002
Noon
489 Minor Hall

Radouil Tzekov, MD, PhD
Assistant Adjunct Professor. Dept. of Ophthalmology, UC Davis
Host: Marilyn Schneck

Title

"The function of the ABCR(ABCA4) gene and protein in the retina and the implications for some retinal diseases"

Abstract

Rim protein (RmP) is an ABC transporter of unknown function in rod outer segment discs. The human gene for RmP (ABCR) is affected in several recessive retinal degenerations.

This seminar will describe the results from studies characterizing the ocular phenotypes of abcr knockout and heterozygotic mice.

Mice lacking RmP show delayed dark adaptation, increased all-trans-retinaldehyde (all-trans-RAL) following light exposure, elevated phosphatidylethanolamine (PE) in outer segments, accumulation of the protonated Schiff base complex of all-trans-RAL and PE (N-retinylidene-PE), and striking deposition of a major lipofuscin fluorophore (A2-E) in retinal pigment epithelium (RPE). These data suggest that RmP functions as an outwardly directed flippase for N-retinylidene-PE. Delayed dark adaptation is likely due to accumulation in discs of the noncovalent complex between opsin and all-trans-RAL. Finally, ABCR-mediated retinal degeneration may result from "poisoning" of the RPE due to A2-E accumulation, with secondary photoreceptor degeneration due to loss of the RPE support role.

The results for heterozygotic abcr mice were similar, showing accumulation of A2PE-H(2) and A2E in abcr+/- retina and RPE, respectively, which was strongly dependent on light exposure. Heterozygous mutants also exhibited delayed recovery of rod sensitivity by ERG. This delay was correlated with elevated levels of all-trans-retinaldehyde (all-trans-RAL) in retina after a photobleach and was not caused by a reduction in quantum-catch due to depletion of 11-cis-retinaldehyde (11-cis-RAL).

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