To evaluate the pleiotropic effects to statins, we analyze the qualitative and quantitative retinal changes in hypercholesterolemic rabbits after a low-dosage statin treatment. For this purpose, New Zealand rabbits were split into three groups: control (G0; n = 10), fed a standard diet; hypercholesterolemic (G1; n = 8), fed a 0.5% cholesterol-enriched diet for 8 months; and statins (G2; n = 8), fed a 0.5% cholesterol-enriched diet for 8 months, together with the administration of statin (pravastatin or fluvastatin sodium) at a dose of 2 mg / kg / day each diet. The retinas were analyzed by transmission electron microscopy and immunohistochemistry (glial fibrillary acidic protein). The retinal thickness of nuclear and plexiform layers were quantified in semi-thin sections. The results revealed that the low-statin-treated rabbits in comparison with the hypercholesterolemic group showed: i) a more preserved structure in all retinal layers; ii) a significant reduction in retinal thickness; iii) a decrease in cell death in the nuclear-and ganglion-cell layers; iv) a reduction of hydropic degeneration in the plexiform and nerve-fiber layers; v) a preservation of astrocytes and of the retinal area occupied by them; and vi) a better-preserved retinal vascular structure. Our findings indicate that low doses of statins can prevent retinal degeneration, acting on retinal macroglia, neurons and retinal vessels, despite that hypercholesterolemia remained unchanged. Thus, the pleiotropic effects of the statins may help safeguard the retinal ultrastructure.

PurposeTo evaluate the pleiotropic effects of low‐dose statins in the morphology of retinal macroglia in long‐term hypercholesterolemic rabbits and to quantify treatment‐induced astrocyte changes.MethodsNew Zealand rabbits were split into three groups: Control (G0; n = 10), fed a standard diet; Hypercholesterolemic (G1; n = 8), fed a 0.5% cholesterol‐enriched diet for 8 months; and Statins (G2; n = 8), fed a 0.5% cholesterol‐enriched diet for 8 months together with the administration of fluvastatin sodium or pravastatin sodium at a dose of 2 mg/Kg/day each. Eyes were processed for immunohistochemistry using anti‐GFAP. The retinal area occupied by astrocytes was quantified.ResultsMüller cells and astrocytes were reactive in G1 and G2. In contrast with G1, no GFAP+ Müller cells forming glial scar‐like structures were detected in G2. In comparison with G0: i) the retinal area occupied by astrocytes associated with the nerve bundles was statistically reduced in G1 (p < 0.006); however, no significant changes were observed in G2; and ii) the retinal area occupied by perivascular astrocytes in G1 was significantly reduced (p < 0.003) due to the disappearance of perivascular astrocytes from the vessels, but significantly increased in G2 (p < 0.030), given that perivascular astrocytes did not disappear from the vessels and were reactive.ConclusionsDespite serum cholesterol values remained unchanged, treatment with low‐dose statins preserved retinal macroglia. The pleiotropic effects of the statins seem to help to prevent astroglial death induced by hypercholesterolemia.