PURPOSE. To determine the cholesterol composition of normal human Bruch's m
embrane and choroid as a function of age and retinal location.
METHODS. Human eyes with grossly normal maculas were preserved <4 hours aft
er donor death. Cryosections of retina and choroid from the macula and temp
oral equator were stained with filipin to reveal esterified (EC) or unester
ified (UC) cholesterol (n = 20, 17-92 years). Filipin fluorescence in Bruch
's membrane was quantified with digital microscopy. Maculas were prepared f
or lipid-preserving electron microscopy (n = 18, 16-87 years) and for ultra
structural analysis after lipid extraction (n = 2, 85 and 89 years). Punche
s of macular Bruch's membrane, 8 mm in diameter, were assayed for cholester
ol content by enzymatic fluorometry (n = 10, >70 years).
RESULTS. EC and UC in Bruch's membrane increased with age in the macula. EC
was sevenfold higher in macula than in periphery. Sixty percent of total c
holesterol was esterified, and Bruch's membrane EC was 16- to 40-fold enric
hed relative to plasma. Solid, 100-nm-diameter particles occupied >30% of t
he inner collagenous layer in eyes >60 years. Cholesterol accumulated in ch
oroidal arteries and in small age-related drusen.
CONCLUSIONS. Human Bruch's membrane ages like arterial intima and other con
nective tissues for which plasma lipoproteins are the known source of extra
cellular cholesterol. Age-related maculopathy and atherosclerotic cardiovas
cular disease may share common pathogenic mechanisms.