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Papers In Press, published online ahead of print January 16, 2005
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Ophthalmology, University of Alabama School of Medicine, Birmingham, AL 35294-0009
Corresponding Author: 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 elevated 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 expression of microsomal triglyceride transfer protein (MTP), required for this process. Consistent with previous evidence for apoB expression, MTP is expressed in RPE, ARPE-19 cell line, and, unexpectedly, retinal ganglion cells, neurons of the central nervous system. De novo synthesis and secretion of neutral lipid byARPE-19 was supported by high levels of radiolabeled EC and triglyceride in medium following 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 (MIM200100; Bassen-Kornzwieg disease), caused by mutations in MTP gene, may involve loss-of-function at the retina.
Revised on December 23, 2004
Accepted on January 5, 2005
Retina expresses microsomal triglyceride transfer protein: implications for age-related maculopathy
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