title: Neuroprotective Effects of Low-Dose Statins in the Retinal Ultrastructure of Hypercholesterolemic Rabbits.
abstract: 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.
authors.affiliation: Instituto de Investigaciones Oftalmológicas Ramón Castroviejo. Universidad Complutense Madrid (UCM), Spain.
authors.forename: Judith
authors.initials: J
authors.lastname: Fernández-Navarro
authors.affiliation: Instituto de Investigaciones Oftalmológicas Ramón Castroviejo. Universidad Complutense Madrid (UCM), Spain.
authors.forename: Pilar
authors.initials: P
authors.lastname: Aldea
authors.affiliation: Instituto de Investigaciones Oftalmológicas Ramón Castroviejo. Universidad Complutense Madrid (UCM), Spain.|Facultad de Óptica y Optometría, UCM, Spain.
authors.forename: Rosa
authors.initials: R
authors.lastname: de Hoz
authors.affiliation: Instituto de Investigaciones Oftalmológicas Ramón Castroviejo. Universidad Complutense Madrid (UCM), Spain.|Facultad de Óptica y Optometría, UCM, Spain.
authors.forename: Juan J
authors.initials: JJ
authors.lastname: Salazar
authors.affiliation: Instituto de Investigaciones Oftalmológicas Ramón Castroviejo. Universidad Complutense Madrid (UCM), Spain.|Facultad de Óptica y Optometría, UCM, Spain.
authors.forename: Ana I
authors.initials: AI
authors.lastname: Ramírez
authors.affiliation: Instituto de Investigaciones Oftalmológicas Ramón Castroviejo. Universidad Complutense Madrid (UCM), Spain.|Facultad de Medicina, UCM, Spain.
authors.forename: Blanca
authors.initials: B
authors.lastname: Rojas
authors.affiliation: Instituto de Investigaciones Oftalmológicas Ramón Castroviejo. Universidad Complutense Madrid (UCM), Spain.|Facultad de Óptica y Optometría, UCM, Spain.
authors.forename: Beatriz I
authors.initials: BI
authors.lastname: Gallego
authors.affiliation: Instituto de Investigaciones Oftalmológicas Ramón Castroviejo. Universidad Complutense Madrid (UCM), Spain.|Facultad de Medicina, UCM, Spain.
authors.forename: Alberto
authors.initials: A
authors.lastname: Triviño
authors.affiliation: Department of Pharmacology, School of Medicine, Complutense University, Madrid, Spain.
authors.forename: Teresa
authors.initials: T
authors.lastname: Tejerina
authors.affiliation: Instituto de Investigaciones Oftalmológicas Ramón Castroviejo. Universidad Complutense Madrid (UCM), Spain.|Facultad de Medicina, UCM, Spain.
authors.forename: José M
authors.identifier: 0000-0002-5145-5094
authors.initials: JM
authors.lastname: Ramírez
mesh_terms: D000818:Animals; D002784:Cholesterol / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D005229:Fatty Acids, Monounsaturated / Q000008:administration & dosage; D000077340:Fluvastatin; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage*; D006937:Hypercholesterolemia / Q000188:drug therapy; D007211:Indoles / Q000008:administration & dosage; D008297:Male; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D017035:Pravastatin / Q000008:administration & dosage; D011817:Rabbits; D012160:Retina / Q000187:drug effects*; D012171:Retinal Vessels / Q000187:drug effects / Q000378:metabolism
chemical_list: D005229:Fatty Acids, Monounsaturated; D005904:Glial Fibrillary Acidic Protein; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007211:Indoles; D018696:Neuroprotective Agents; D000077340:Fluvastatin; D002784:Cholesterol; D017035:Pravastatin