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J. Biol. Chem., Vol. 276, Issue 15, 11766-11774, April 13, 2001
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From the Departments of A large body of experimental and clinical data
have documented the damaging effects of light exposure on photoreceptor
cells although the identities of the biologically relevant molecular targets of photodamage are still uncertain. Several lines of evidence point to retinoids or retinoid derivatives as chromophores that can
mediate light damage. We report here that ABCR, a
photoreceptor-specific transporter involved in the recycling of
all-trans-retinal, is unusually sensitive to photooxidation
damage mediated by all-trans-retinal in vitro.
Partial loss of ABCR function is responsible for Stargardt macular
dystrophy, which is associated with accumulation of A2E, a diretinoid
adduct within the retinal pigment epithelium. Photodamage to ABCR
causes it to aggregate in SDS gels and results in the loss of
retinal-stimulated ATPase activity. Peripherin/RDS and ROM-1, two
structural proteins that colocalize with ABCR at the outer
segment disc rim, are also significantly more susceptible to
all-trans-retinal-mediated photodamage than are the major
proteins from the rod outer segment. These observations imply that
there may be specific protein targets of photodamage within the outer segment, and they may be especially relevant to assessing the risk of
light exposure in those individuals who already have diminished ABCR
activity due to mutation in one or both copies of the ABCR gene.
ABCR, the ATP-binding Cassette Transporter Responsible for
Stargardt Macular Dystrophy, Is an Efficient Target of
All-trans-retinal-mediated Photooxidative Damage in
Vitro
IMPLICATIONS FOR RETINAL DISEASE*
§ and§¶
**
Molecular Biology and
Genetics, ¶ Neuroscience, and Ophthalmology and the
§ Howard Hughes Medical Institute, Johns Hopkins University
School of Medicine, Baltimore, Maryland 21205
*
This work was supported by the Howard Hughes Medical
Institute and the National Eye Institute National Institutes of Health.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.
Copyright © 2001 by The American Society for Biochemistry and Molecular Biology, Inc.
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