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Papers In Press, published online ahead of print December 26, 2001
Department of Ophthalmology, Columbia University, New York, NY 10032
Corresponding Author: jrs88{at}columbia.edu
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. While 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 which 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 RPE lipofuscin, A2E isomers with cis olefins at positions other than the C13-C14 double bond, are also described.
J. Biol. Chem, 10.1074/jbc.M108981200
Submitted on September 17, 2001
Revised on December 10, 2001
Accepted on December 21, 2001
Biosynthetic studies of A2E, A major fluorophore of RPE lipofuscin
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