Intravitreal triamcinolone acetonide, retinal microglia and retinal ganglion cell apoptosis in the optic nerve crush model

Acta Ophthalmol. 2016 Aug;94(5):e305-11. doi: 10.1111/aos.12698. Epub 2015 Feb 23.

Abstract

Purpose: To evaluate the effect of intravitreal triamcinolone acetonide (TA) on the activation of retinal microglia cells (RMGCs) and survival of retinal ganglion cells (RGCs) in an optic nerve crush (ONC) model.

Methods: Adult female Sprague-Dawley rats underwent a standardized ONC and either received an intravitreal injection of TA (TA group) or of phosphate-buffered saline (PBS, PBS group) in the right eyes. At 1, 3, 7, 14 and 28 days after the ONC, the animals were killed. The retinas were examined by immunohistochemistry, light microscopy, Western blot or retrograde labelling of RGCs by fluorogold injected into the superior colliculi.

Results: The TA group as compared to the PBS control group showed a significantly (p < 0.0001) lower density of activated RMGCs, at 14 days [4.2 ± 1.6 versus 9.3 ± 2.2 cells/high-power microscopic field (HPF)] and at 28 days (2.3 ± 1.1 versus 4.4 ± 1.5 cells/HPF), and with a significantly lower expression of inflammatory factors. Central density of RGCs as stained by haematoxylin-eosin or by fluorogold was significantly (all p < 0.05) more reduced in the PBS group than in the TA group at days 14 and 28 after baseline. The survival rate (cell density in the study eye as compared to cell density in the contralateral unaffected eye) was significantly higher in the TA group than in the PBS group on days 14 (58% versus 45%; p = 0.003) and 28 (52% versus 41%; p = 0.022).

Conclusions: Intravitreal TA as compared to intravitreal PBS was associated with a lower density of activated RMGCs and a higher density of surviving RGCs in an ONC model.

Keywords: intravitreal triamcinolone; optic nerve; optic nerve crush; retinal ganglion cells; retinal microglial cells.

MeSH terms

  • Animals
  • Apoptosis / drug effects*
  • Biomarkers / metabolism
  • Blotting, Western
  • Cell Count
  • Cell Survival / drug effects
  • Disease Models, Animal
  • Female
  • Fluorescent Antibody Technique, Indirect
  • Glucocorticoids / pharmacology*
  • Intercellular Adhesion Molecule-1 / metabolism
  • Intravitreal Injections
  • Microglia / metabolism
  • Microglia / pathology*
  • Microscopy, Confocal
  • Nerve Crush
  • Nitric Oxide Synthase Type II / metabolism
  • Optic Nerve Diseases / metabolism
  • Optic Nerve Diseases / prevention & control*
  • Rats, Sprague-Dawley
  • Retinal Ganglion Cells / metabolism
  • Retinal Ganglion Cells / pathology*
  • Retinal Neurons / metabolism
  • Retinal Neurons / pathology*
  • Triamcinolone Acetonide / pharmacology*
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Biomarkers
  • Glucocorticoids
  • Tumor Necrosis Factor-alpha
  • Intercellular Adhesion Molecule-1
  • Nitric Oxide Synthase Type II
  • Nos2 protein, rat
  • Triamcinolone Acetonide