Effect of neuroprotective statins in retina: A hypercholesterolemic rabbit model

Purpose The aim of the present study was to analyze qualitative and quantitative retinal changes in hypercholesterolemic rabbits after a low-dosage statin treatment and to evaluate their possible neuroprotective effect on the retina. Methods New Zealand rabbits were divided into three groups: Control (G0; n=6), fed a standard diet; Hypercholesterolemic (G1, n=6), fed a 0.5% cholesterol-enriched diet for 8 months; and Statins (G2; n=6), fed a 0.5% cholesterol-enriched diet for 8 months plus administration of fluvastatin sodium or pravastatin sodium at a dosage of 2 mg/Kg/day each. Eyes were processed and analyzed for transmission-electron microscopy. Semi-thin sections were used to quantify cell number and thickness of retinal layers (excluding retinal pigment epithelium and nerve-fiber layer) under light microscopy. Results G1 and G2, in comparison to G0, had a decreased cell number in the outer nuclear layer (ONL) (p<0.05 and p<0.005, respectively). No differences were detected in the inner nuclear layer or ganglion-cell layer among the study groups. In G2, the ultrastructural cell morphology was similar to G0 and there were fewer signs of necrosis and apoptosis than in G1. Although the ONL cell number was decreased in G1, the retinal thickness in this group showed no differences in comparison to G0 due to retinal edema. Retinal thickness in G2 was reduced with respect to G1 (p<0.05) because of the absence of retinal edema, and to G0 (p<0.05) due to ONL cell loss. Conclusion Low-dosage statins did not prevent ONL cell loss but preserved the normal ultrastructure of the remaining retinal neurons and avoided hypercholesterolemia-induced retinal edema.