Early Change of Vascular Permeability in Hypercholesterolemic Rabbits

Abstract

Abstract To study the effect of hyperlipidemia on vascular permeability, serial anterior chamber fluorophotometric examinations were carried out on 33 control rabbits (group 1) and 32 diet-induced hypercholesterolemic (group 2) rabbits. Changes in the blood-aqueous barrier function associated with total serum cholesterol (CHO) and triglyceride (TG) levels were studied at the beginning of the study and every 2 weeks thereafter for up to 16 weeks following 0.5% cholesterol–enriched diet feeding. Concurrently, a slit-lamp biomicroscope was used to examine the iris for evidence of atheromatous plaque. In group 1, the CHO level decreased slightly during the first 6 weeks and remained rather steady thereafter. The status of the blood-aqueous barrier correlated significantly with serum CHO and TG levels ( r =.46, P <.001; r =.23, P =.01, respectively). In group 2, CHO and TG levels increased significantly after 2 and 8 weeks of cholesterol-enriched diet feeding, respectively. The blood-aqueous barrier also became more permeable than that in group 1 after 2 weeks’ and increased above its baseline level after 6 weeks’ feeding. Both CHO and TG levels correlated well with the degree of blood-aqueous barrier breakdown ( r =.51, P <.001; r =.25, P <.001, respectively). The first evidence of iridic lipid-streak deposition was noted at 7.6±0.7 weeks, while definite iridic atheromatous plaque appeared 11.2±0.7 weeks after feeding. The change in the blood-aqueous barrier also correlated well with the semiquantitative score of iridic plaque ( r =.58, P <.001) and usually preceded visual evidence of plaque formation. Pathological examinations of the eye showed marked foam cell infiltration in the stroma of the ciliary body, the ciliary process, and iris stroma, similar to changes in atheromas of the thoracic aorta after 16 weeks of feeding. In conclusion, anterior segment fluorophotometry is a valuable tool for detecting vascular integrity in vivo. These results suggest that the permeability change correlates well with serum CHO level and occurs in the very early stages of atherogenesis.