Simvastatin improves retinal ganglion cell survival and spatial vision after acute retinal ischemia/reperfusion in mice

Invest Ophthalmol Vis Sci. 2011 Apr 20;52(5):2606-18. doi: 10.1167/iovs.10-6005.

Abstract

Purpose: The major aims of this study were to evaluate the effect of retinal ischemia by behavioral testing and histologic analyses, to visualize ischemia-induced changes of cortical activity by optical imaging of intrinsic signals, and to test the therapeutic effectiveness of simvastatin.

Methods: Retinal ischemia was induced monocularly by elevating intraocular pressure. Visual function was tested behaviorally with a virtual reality optomotor system, physiologically with optical imaging of intrinsic signals, and histologically by counting the surviving retinal ganglion cells (RGCs) in the same animal.

Results: Visual acuity (-38%) and contrast sensitivity (-78%) were significantly reduced 6 days after ischemia compared with controls. The number of RGCs was reduced by 16%. In contrast, optical imaging revealed essentially unchanged cortical activity maps in spite of the lesion. Treatment of mice with simvastatin applied after the ischemic insult significantly improved both visual function as measured behaviorally (~95% visual acuity, ~165% contrast sensitivity) and RGC survival (~30%) compared with vehicle-treated animals (~42% visual acuity, ~85% contrast sensitivity).

Conclusions: This specific combination of behavioral measurements of visual function, cortical activity imaging, and histologic analyses is ideally suited to follow ischemia-induced changes and to monitor the effect of therapeutic approaches. Statin therapy may be a promising pharmacologic tool for the treatment of acute retinal ischemia in particular because, in our study, simvastatin was applied after ischemia, a treatment regimen with much greater clinical relevance than preventive administration, as in previous studies.

MeSH terms

  • Acute Disease
  • Animals
  • Behavior, Animal
  • Cell Count
  • Cell Survival
  • Contrast Sensitivity / physiology*
  • Disease Models, Animal
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Reperfusion Injury / physiopathology
  • Reperfusion Injury / prevention & control*
  • Retinal Diseases / physiopathology
  • Retinal Diseases / prevention & control*
  • Retinal Ganglion Cells / drug effects*
  • Retinal Ganglion Cells / physiology
  • Retinal Vessels
  • Simvastatin / therapeutic use*
  • Spatial Behavior / physiology*
  • Vision, Ocular / physiology*
  • Visual Acuity / physiology*

Substances

  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Simvastatin