Lipid A dependence of the ocular response to circulating endotoxin in rabbits

The effects of bacterial lipopolysaccharides on ocular vascular permeability were measured after their intravenous injection in rabbits. Alterations in ocular vascular permeability were quantitated by the accumulation of 125I-labeled albumin in the enucleated eye compared with that in heart blood (ocular albumin space). Two lipopolysaccharides extracted from Escherichia coli O111:B4, one with high lipid A content and one with high polysaccharide content, were tested initially, and the one with greater lipid A was 200 times more effective in producing an alteration in ocular vascular permeability. Lipopolysaccharide from a rough strain, Salmonella minnesota (R595), containing lipid A primarily, as well as a purified lipid A extracted from +595, were also effective. But an extract of the protein associated with lipid A was without significant effect. In vitro pretreatment of the lipopolysaccharides with polymyxin B, an inhibitor of the biological activity of lipid A through direct binding, could abrogate the ocular response. These results indicate the paramount importance of the lipid A moiety in the ocular response to circulating endotoxin.