Retina expresses microsomal triglyceride transfer protein: implications for age-related maculopathy.
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.
Li
Chuan-Ming
CM
Department of Ophthalmology, University of Alabama School of Medicine, Birmingham, AL, USA.
Presley
J Brett
JB
Zhang
Xueming
X
Dashti
Nassrin
N
Chung
Byong Hong
BH
Medeiros
Nancy E
NE
Guidry
Clyde
C
Curcio
Christine A
CA
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000502:physiology; D000818:Animals; D001055:Apolipoproteins B / Q000235:genetics / Q000378:metabolism; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D005786:Gene Expression Regulation; D006801:Humans; D008268:Macular Degeneration / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008854:Microscopy, Electron; D008875:Middle Aged; D010857:Pigment Epithelium of Eye / Q000378:metabolism; D012160:Retina / Q000378:metabolism* / Q000473:pathology; D013552:Swine
D001055:Apolipoproteins B; D002352:Carrier Proteins; C106092:microsomal triglyceride transfer protein