Pleiotropic Effects of Choroidal Damage in Hypercholesterolemic Rabbits. A Morphometric Study

Abstract

Purpose: : To describe the ultrastructural changes in the choroid of hipercholesterolemic rabbits after a low-dose statin treatment and to evaluate some pleiotropic effects of these drugs on the morphology of endothelial cells (EC) and vascular smooth-muscle cells (VSMC).

Methods: : New Zealand rabbits were divided into three groups: G0, fed a standard diet; G1, fed a 0.5% cholesterol-enriched diet for 8 months; and G2, fed a 0.5% cholesterol-enriched diet for 8 months plus administration of fluvastatin sodium or pravastatin sodium at a dose of 2 mg/Kg/day each. Eyes were processed for transmission-electron microscopy.

Results: : Plasma-lipid levels did not statistically differ between statin-treated and -untreated animals. However, the signs of necrosis observed in EC and VSMC of G1 contrasted with the preservation of cytoplasmic organelles, caveolar system and other ultrastructural features in G2. G1 had a build-up of lipids at the suprachoroidea that compressed the vascular layers. G2 had a decreased of suprachoroidal foam cells and lipids in the vascular layers, and the vascular lumens were opened. Bruch’s membrane in G2 contained fewer lipids and more collagen than in G1. In comparison with G1, G2 had in both the periphery and the medullated nerve-fibre region (MNFR): i) a reduction in the thickness of the sclera-suprachoroidea complex (p< 0.000); ii) a increment in the thickness of the vascular layers (p< 0.000) and iii) a reduction in the thickness of Bruch’s membrane (p< 0.000). In the MNFR, the thickness of the Bruch’s membrane in G2 did not differ from control (p> 0.05).

Conclusions: : Treatment with a low dosage of fluvastatin sodium or pravastatin sodium reduced the build-up of lipids and the macrophages in the choroid and restored the vascular lumens of choroidal vessels independently of the cholesterol effect. The normal ultrastructural features of choroidal EC and VSMC in statin-treated animals suggest that the endothelial function is preserved and the ischemia reduced.

Keywords: ischemia • lipids • microscopy: electron microscopy