Low-dosage statins reduce choroidal damage in hypercholesterolemic rabbits.
OBJECTIVE
To describe the ultrastructural changes in the choroid of long-term hypercholesterolemic rabbits after a low-dosage 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
G1 had a lipid build-up at the suprachoroidea that compressed the vascular layers with the lumens of the vessels to the point of collapse in some instances. By contrast, G2 underwent a substantial decrease in suprachoroidal foam cells and of lipids in the vascular layers while the vascular lumens were normal. The preservation of cytoplasmic organelles, caveolar system and other ultrastructural features of EC and VSMC in G2 contrasted with the numerous signs of necrosis observed in G1. Bruch's membrane (BM) in G2 contained fewer lipids and more collagen than in G1.


CONCLUSIONS
Treatment with a low dosage of fluvastatin sodium or pravastatin sodium reduced the lipid build-up as well as 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 ischaemia reduced.
Rojas
Blanca
B
Institute for Ophthalmic Research, Ramón Castroviejo, Complutense University, Madrid, Spain.
Ramírez
Ana I
AI
Salazar
Juan J
JJ
de Hoz
Rosa
R
Redondo
Alma
A
Raposo
Rafaela
R
Mendez
Teresa
T
Tejerina
Teresa
T
Triviño
Alberto
A
Ramírez
Jose M
JM
D000818:Animals; D000924:Anticholesteremic Agents / Q000008:administration & dosage*; D002784:Cholesterol / Q000097:blood; D002791:Cholesterol, Dietary / Q000008:administration & dosage; D002829:Choroid / Q000187:drug effects* / Q000648:ultrastructure; D015862:Choroid Diseases / Q000188:drug therapy* / Q000473:pathology; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000648:ultrastructure; D005229:Fatty Acids, Monounsaturated / Q000008:administration & dosage*; D000077340:Fluvastatin; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage*; D006937:Hypercholesterolemia / Q000188:drug therapy* / Q000473:pathology; D007211:Indoles / Q000008:administration & dosage*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000648:ultrastructure; D017035:Pravastatin / Q000008:administration & dosage*; D011817:Rabbits; D014280:Triglycerides / Q000097:blood
D000924:Anticholesteremic Agents; D002791:Cholesterol, Dietary; D005229:Fatty Acids, Monounsaturated; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007211:Indoles; D014280:Triglycerides; D000077340:Fluvastatin; D002784:Cholesterol; D017035:Pravastatin