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Originally published In Press as doi:10.1074/jbc.M108981200 on December 26, 2001

J. Biol. Chem., Vol. 277, Issue 9, 7183-7190, March 1, 2002
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Biosynthetic Studies of A2E, a Major Fluorophore of Retinal Pigment Epithelial Lipofuscin*

Shimon Ben-ShabatDagger , Craig A. ParishDagger , Heidi R. VollmerDagger , Yasuhiro ItagakiDagger , Nathan FishkinDagger , Koji NakanishiDagger §, and Janet R. Sparrow||

From the Departments of Dagger  Chemistry and  Ophthalmology, Columbia University, New York, New York 10028

We have examined questions related to the biosynthesis of A2E, a fluorophore that accumulates in retinal pigment epithelial cells with aging and in some retinal disorders. The use of in vitro preparations revealed that detectable levels of A2-PE, the A2E precursor, are formed within photoreceptor outer segments following light-induced release of endogenous all-trans-retinal. Moreover, experiments in vivo demonstrated that the formation of A2-PE in photoreceptor outer segment membrane was augmented by exposing rats to bright light. Whereas the generation of A2E from A2-PE by acid hydrolysis was found to occur very slowly, the detection in outer segments of a phosphodiesterase activity that can convert A2-PE to A2E may indicate that some portion of the A2-PE that forms in the outer segment membrane may undergo hydrolytic cleavage before internalization by the retinal pigment epithelial cell. The identities of additional minor components of retinal pigment epithelium lipofuscin, A2E isomers with cis olefins at positions other than the C13-C14 double bond, are also described.

* This work was supported in part by National Institutes of Health Grants 34509 (to K. N.) and EY12951 (to J. R. S.), the Charina Foundation (J. R. S.), the Macula Vision Research Foundation (J. R. S.) and unrestricted funds from Research to Prevent Blindness.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

§ To whom correspondence may be addressed: Dept. of Chemistry, Columbia University, New York, NY 10027. Tel: 212-854-2169; Fax: 212-932-8273; E-mail: kn5@columbia.edu.

|| Recipient of a Research to Prevent Blindness Lew R. Wasserman Merit Award. To whom correspondence may be addressed: Dept. of Ophthalmology, Columbia University, New York, NY 10032. Tel.: 212-305-9944; Fax: 212-305-9638; E-mail: jrs88@columbia.edu.

Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.
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