Apolipoprotein B in cholesterol-containing drusen and basal deposits of human eyes with age-related maculopathy.
Lipids accumulate in Bruch's membrane (BrM), a specialized vascular intima of the eye, and in extracellular lesions associated with aging and age-related maculopathy (ARM). We tested the hypothesis that ARM and atherosclerotic cardiovascular disease share molecules and mechanisms pertaining to extracellular lipid accumulation by localizing cholesterol and apolipoprotein B (apo B) in BrM, basal deposits, and drusen. Human donor eyes were preserved <4 hours postmortem and cryosectioned. Sections were stained with traditional lipid stains and filipin for esterified and unesterified cholesterol or probed with antibodies to apo B, apo E, and apo C-III. Normal adult retinal pigment epithelium (RPE) was subjected to RT-PCR and Western blot analysis for apolipoprotein mRNA and protein. Esterified and unesterified cholesterol was present in all drusen and basal deposits of ARM and normal eyes. Both apo B and apo E but not apo C-III were found in BrM, drusen, and basal deposits. Fewer macular drusen were stained by traditional lipid stains and apolipoprotein antibodies than peripheral drusen. RPE contained apo B and apo E mRNA and protein. Finding cholesterol and apo B in sub-RPE deposits links ARM with important molecules and mechanisms in atherosclerosis initiation and progression. The combination of apo B mRNA and protein in RPE raises the possibility that intraocular assembly of apo B-containing lipoproteins is a pathway involved in forming cholesterol-enriched lesions in ARM.
Malek
Goldis
G
Department of Ophthalmology, Vision Science Training Program, University of Alabama at Birmingham, Birmingham, AL 35294-0009, USA.
Li
Chuan-Ming
CM
Guidry
Clyde
C
Medeiros
Nancy E
NE
Curcio
Christine A
CA
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging; D000595:Amino Acid Sequence; D053304:Apolipoprotein C-II; D001055:Apolipoproteins B / Q000032:analysis* / Q000235:genetics*; D001056:Apolipoproteins C / Q000032:analysis; D001057:Apolipoproteins E / Q000235:genetics; D002784:Cholesterol / Q000032:analysis*; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D008268:Macular Degeneration / Q000235:genetics / Q000473:pathology*; D008297:Male; D010857:Pigment Epithelium of Eye / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D012016:Reference Values; D015593:Retinal Drusen / Q000235:genetics / Q000473:pathology*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D053304:Apolipoprotein C-II; D001055:Apolipoproteins B; D001056:Apolipoproteins C; D001057:Apolipoproteins E; D012333:RNA, Messenger; D002784:Cholesterol