Neuroprotective Effects of Low-Dose Statins in the Retinal Ultrastructure of Hypercholesterolemic Rabbits

PLoS One. 2016 May 4;11(5):e0154800. doi: 10.1371/journal.pone.0154800. eCollection 2016.

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.

MeSH terms

  • Animals
  • Cholesterol / metabolism
  • Endothelium, Vascular / drug effects
  • Endothelium, Vascular / metabolism
  • Fatty Acids, Monounsaturated / administration & dosage
  • Fluvastatin
  • Glial Fibrillary Acidic Protein / metabolism
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / administration & dosage*
  • Hypercholesterolemia / drug therapy
  • Indoles / administration & dosage
  • Male
  • Neuroprotective Agents / administration & dosage*
  • Pravastatin / administration & dosage
  • Rabbits
  • Retina / drug effects*
  • Retinal Vessels / drug effects
  • Retinal Vessels / metabolism

Substances

  • Fatty Acids, Monounsaturated
  • Glial Fibrillary Acidic Protein
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Indoles
  • Neuroprotective Agents
  • Fluvastatin
  • Cholesterol
  • Pravastatin

Grants and funding

This work was supported by RETICs Patología Ocular del Envejecimiento, Calidad Visual y Calidad de Vida (Grant RD07/0062/0000, Instituto de Salud Carlos III, Ministerio de Sanidad y Consumo) (RdH, JJS, AIR, BR, BIG, AT, JMR); Fundación Mutua Madrileña (Grant 4131173) (RdH, JJS, AIR, BR, AT, JMR); Programa de Creación y Consolidación de Grupos de Investigación Banco Santander Central Hispano – Universidad Complutense GR3/14 (RdH, JJS, AIR, BR, AT, JMR). RETICs RECAVA (Grant RD06⁄0014 ⁄ 0007, Instituto de Salud Carlos III, Ministerio de Sanidad y Consumo) (TT).