Purpose: Breakdown of the blood-retinal barrier is a major cause of vi
sual loss in diseases such as diabetic retinopathy, age-related macula
r degeneration and retinal vein occlusion. Methods: Human serum, fract
ionated by gel filtration, was screened for factors that enhance barri
er activity by measuring electrical resistance across monolayers of hu
man umbilical vein endothelial cells. Results: Two peaks of barrier-en
hancing activity were detected. The larger peak was broad, contained a
preponderance of albumin and increased barrier activity to 183% of co
ntrols. The barrier-enhancing properties of the larger peak however ap
peared to be associated with proteins in general and not just albumin.
The fractions associated with elution of the larger peak induced maxi
mal increase in resistance in under 1 h, relative to controls. The sma
ller peak was associated with molecular weights much smaller than thos
e of proteins.