出版社：American Society for Biochemistry and Molecular Biology
摘要：The principal extracellular lesions of age-related maculopathy(ARM), the leading cause of vision loss in the elderly, involveBruch's membrane (BrM), a thin vascular intima between the retinalpigment epithelium (RPE) and its blood supply. With age, 80–100nm solid particles containing esterified cholesterol (EC) accumulatein normal BrM, and apolipoprotein B (apoB) immunoreactivityis detectable in BrM- and ARM-associated lesions. Yet littleevidence indicates that increased plasma cholesterol is a riskfactor for ARM. To determine if RPE is capable of assemblingits own apoB-containing lipoprotein, we examined RPE for theexpression of microsomal triglyceride transfer protein (MTP),which is required for this process. Consistent with previousevidence for apoB expression, MTP is expressed in RPE, the ARPE-19cell line, and, unexpectedly, retinal ganglion cells, whichare neurons of the central nervous system. De novo synthesisand secretion of neutral lipid by ARPE-19 was supported by highlevels of radiolabeled EC and triglyceride in medium after supplementationwith oleate. Lipoprotein assembly and secretion is implicatedas a constitutive retinal function and a plausible candidatemechanism involved in forming extracellular cholesterol-containinglesions 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 lossof 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
