Neuroprotective Effect of Statins in a Rat Model of Chronic Ocular Hypertension

Int J Mol Sci. 2021 Nov 19;22(22):12500. doi: 10.3390/ijms222212500.

Abstract

Glaucoma is an optic neuropathy in which the degeneration of retinal ganglion cells (RGCs) results in irreversible vison loss. Therefore, neuroprotection of RGCs from glaucomatous afflictions is crucial for glaucoma treatment. In this study, we aimed to investigate the beneficial effects of statins in the protection of RGCs using a rat model. Glaucomatous injury was induced in rats by chronic ocular hypertension (OHT) achieved after performing a circumlimbal suture. The rats were given either statins such as simvastatin and atorvastatin or a solvent weekly for 6 weeks. Retina sections underwent hematoxylin and eosin, Brn3a, or cleaved casepase-3 staining to evaluate RGC survival. In addition, modulation of glial activation was assessed. While the retinas without statin treatment exhibited increased RGC death due to chronic OHT, statins promoted the survival of RGCs and reduced apoptosis. Statins also suppressed chronic OHT-mediated glial activation in the retina. Our results demonstrate that statins exert neuroprotective effects in rat retinas exposed to chronic OHT, which may support the prospect of statins being a glaucoma treatment.

Keywords: glaucoma; neuroprotection; ocular hypertension; retinal ganglion cell; statin.

MeSH terms

  • Animals
  • Disease Models, Animal
  • Glaucoma / drug therapy*
  • Glaucoma / genetics
  • Glaucoma / pathology
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology*
  • Intraocular Pressure / drug effects
  • Neuroprotection / genetics
  • Neuroprotective Agents / pharmacology
  • Ocular Hypertension / drug therapy*
  • Ocular Hypertension / genetics
  • Ocular Hypertension / pathology
  • Optic Nerve / drug effects
  • Optic Nerve / pathology
  • Optic Nerve Diseases / drug therapy
  • Optic Nerve Diseases / genetics
  • Optic Nerve Diseases / pathology
  • Rats
  • Retina / drug effects
  • Retina / pathology
  • Retinal Degeneration / drug therapy*
  • Retinal Degeneration / genetics
  • Retinal Degeneration / pathology
  • Retinal Ganglion Cells / drug effects
  • Retinal Ganglion Cells / pathology
  • Transcription Factor Brn-3A / chemistry
  • Transcription Factor Brn-3A / isolation & purification

Substances

  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Neuroprotective Agents
  • POU4F1 protein, human
  • Transcription Factor Brn-3A