J. Lipid Res.
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Originally published In Press as doi:10.1194/jlr.M400428-JLR200 on January 16, 2005

Papers In Press, published online ahead of print April 1, 2005
J. Lipid Res., doi:10.1194/jlr.M400428-JLR200
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Journal of Lipid Research, Vol. 46, 628-640, April 2005
Copyright © 2005 by American Society for Biochemistry and Molecular Biology

Retina expresses microsomal triglyceride transfer protein: implications for age-related maculopathy

Chuan-Ming Li*, J. Brett Presley*, Xueming Zhang*, Nassrin Dashti{dagger}, Byong Hong Chung{dagger}, Nancy E. Medeiros§, Clyde Guidry* and Christine A. Curcio1,*

* Department of Ophthalmology, Department of Medicine, University of Alabama School of Medicine, Birmingham, AL
{dagger} Division of Gerontology and Atherosclerosis Research Program, Department of Medicine, University of Alabama School of Medicine, Birmingham, AL
§ Retina Specialists of North Alabama, Huntsville, AL

Published, JLR Papers in Press, January 16, 2005. DOI 10.1194/jlr.M400428-JLR200

The online version of this article (available at http://www.jlr.org) contains an additional table.

1 To whom correspondence should be addressed. e-mail: curcio{at}uab.edu

The principal extracellular lesions of age-related maculopathy (ARM), the leading cause of vision loss in the elderly, involve Bruch's membrane (BrM), a thin vascular intima between the retinal pigment epithelium (RPE) and its blood supply. With age, 80–100 nm solid particles containing esterified cholesterol (EC) accumulate in normal BrM, and apolipoprotein B (apoB) immunoreactivity is detectable in BrM- and ARM-associated lesions. Yet little evidence indicates that increased plasma cholesterol is a risk factor for ARM. To determine if RPE is capable of assembling its own apoB-containing lipoprotein, we examined RPE for the expression of microsomal triglyceride transfer protein (MTP), which is required for this process. Consistent with previous evidence for apoB expression, MTP is expressed in RPE, the ARPE-19 cell line, and, unexpectedly, retinal ganglion cells, which are neurons of the central nervous system. De novo synthesis and secretion of neutral lipid by ARPE-19 was supported by high levels of radiolabeled EC and triglyceride in medium after supplementation with oleate. Lipoprotein assembly and secretion is implicated as a constitutive retinal function and a plausible candidate mechanism involved in forming extracellular cholesterol-containing lesions in ARM.

The pigmentary retinopathy and neuropathy of abetalipoproteinemia (Mendelian Inheritance of Man 200100; Bassen-Kornzwieg disease), which is caused by mutations in the MTP gene, may involve loss of function at the retina.

Abbreviations: ABL, abetalipoproteinemia; apoB, apolipoprotein B; apoBEC-1, apolipoprotein B-editing complex-1; ARM, age-related maculopathy; BrM, Bruch's membrane; EC, esterified cholesterol; ESI/MS, electrospray ionization mass spectrometry; INL, inner nuclear layer; MCT3, monocarboxylate transporter 3; MTP, microsomal triglyceride transfer protein; OS, outer segments of photoreceptors; RGC, retinal ganglion cell; RPE, retinal pigment epithelium; TC, total cholesterol; TG, triglyceride; UC, unesterified cholesterol

Supplementary key words lipoprotein assembly • esterified cholesterol • retinal pigment epithelium • Bruch's membrane • abetalipoproteinemia


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