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Originally published In Press as doi:10.1074/jbc.M802981200 on July 7, 2008

J. Biol. Chem., Vol. 283, Issue 36, 25091-25102, September 5, 2008
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Retinyl Ester Homeostasis in the Adipose Differentiation-related Protein-deficient Retina*Formula

Yoshikazu Imanishi{ddagger}12, Wenyu Sun{ddagger}1, Tadao Maeda{ddagger}§, Akiko Maeda{ddagger}, and Krzysztof Palczewski{ddagger}3

From the {ddagger}Department of Pharmacology and §Department of Ophthalmology, Case Western Reserve University, Cleveland, Ohio 44106

The retinal pigmented epithelium (RPE) plays an essential role in vision, including storing and converting retinyl esters of the visual chromophore, 11-cis-retinal. Retinyl ester storage structures (RESTs), specialized lipid droplets within the RPE, take up retinyl esters synthesized in the endoplasmic reticulum. Here we report studies of mice lacking exons 2 and 3 of the gene encoding adipose differentiation-related protein (Adfp), a structural component of RESTs. We found that dark adaptation was slower in Adfp{Delta}2-3/{Delta}2-3 than in Adfp+/+ mice and that Adfp{Delta}2-3/{Delta}2-3 mice had consistently delayed clearances of all-trans-retinal and all-trans-retinol from rod photoreceptor cells. Two-photon microscopy revealed aberrant trafficking of all-trans-retinyl esters in the RPE of Adfp{Delta}2-3/{Delta}2-3 mice, a problem caused by abnormal maintenance of RESTs in the dark-adapted state. Retinyl ester accumulation was also reduced in Adfp{Delta}2-3/{Delta}2-3 as compared with Adfp+/+ mice. These observations suggest that Adfp plays a unique role in vision by maintaining proper storage and trafficking of retinoids within the eye.


Received for publication, April 17, 2008 , and in revised form, June 9, 2008.

* This work was supported, in whole or in part, by National Institutes of Health Grants EY009339 and P30 EY11373. This work was also supported by the Klaus Tschira Foundation, the European Life Scientist Organization, and by an unrestricted grant from Amgen Inc. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Formula The on-line version of this article (available at http://www.jbc.org) contains supplemental Figs.1-5 and Movies 1 and 2.

1 Both authors contributed equally to this work.

2 To whom correspondence may be addressed: Dept. of Pharmacology, School of Medicine, Case Western Reserve University, Wood Bldg., 10900 Euclid Ave, Cleveland, OH 44106-4965. E-mail: yxi19{at}case.edu.

3 To whom correspondence may be addressed: Dept. of Pharmacology, School of Medicine, Case Western Reserve University, 10900 Euclid Ave, Cleveland, OH 44106-4965. Tel.: 216-368-4631; Fax: 216-368-1300; E-mail: kxp65{at}case.edu.


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