Ischemia results 3 months later in altered ERG, degeneration of inner layers, and deafferented tectum: neuroprotection with brimonidine

Invest Ophthalmol Vis Sci. 2005 Oct;46(10):3825-35. doi: 10.1167/iovs.05-0392.

Abstract

Purpose: To investigate the long-term effects of transient ligature of the ophthalmic vessels (LOV) on the inner and outer retina as well as on retinotectal projection, and whether brimonidine (BMD) has protective effects.

Methods: In adult rats, the left eye was subjected to 90 minutes of LOV. One hour before ischemia, 2 drops of saline alone (vehicle group) or saline containing 0.5% brimonidine (BMD group) were instilled in the left eye. The effects of LOV on the inner and outer retina were assessed with ERG recordings of a- and b-wave amplitudes at 1, 8, and 12 weeks after LOV and with analysis of layer thickness in paraffin sections. The retinotectal projection was orthogradely labeled with cholera toxin subunit B (CTB) injected in the left eye and measured in serial coronal sections of the superior colliculus.

Results: There were significant reductions in the mean b-wave amplitudes of the ischemic eyes at 8 and 12 weeks after LOV in the vehicle-treated group of animals, but not in the BMD-treated group. The thickness of the inner nuclear and inner plexiform layers of the vehicle-treated group of retinas had decreased to approximately 71% of the thicknesses in the BMD-treated groups. Three months after LOV, the mean volume of the retinotectal projection in the vehicle- or BMD-treated group of animals had decreased to approximately 54% or 83%, respectively, of the mean values found in the control group of animals.

Conclusions: LOV induces degeneration of the inner retinal layers and the retinotectal projection 3 months after the insult. BMD administration significantly protected against LOV-induced retinal damage and degeneration of retinal projection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brimonidine Tartrate
  • Electroretinography
  • Female
  • Ischemia / physiopathology
  • Ischemia / prevention & control*
  • Ligation
  • Nerve Degeneration / prevention & control
  • Neuroprotective Agents / therapeutic use*
  • Ophthalmic Artery / surgery
  • Quinoxalines / therapeutic use*
  • Rats
  • Rats, Sprague-Dawley
  • Retina / drug effects*
  • Retina / physiopathology
  • Retinal Degeneration / etiology
  • Retinal Degeneration / physiopathology
  • Retinal Degeneration / prevention & control*
  • Retinal Ganglion Cells / drug effects
  • Retinal Ganglion Cells / physiology
  • Retinal Vessels / physiopathology*
  • Superior Colliculi / drug effects*
  • Superior Colliculi / physiopathology
  • Time Factors
  • Visual Pathways / drug effects
  • Visual Pathways / physiopathology

Substances

  • Neuroprotective Agents
  • Quinoxalines
  • Brimonidine Tartrate