Retinal ganglion cell morphology after optic nerve crush and experimental glaucoma

Invest Ophthalmol Vis Sci. 2012 Jun 22;53(7):3847-57. doi: 10.1167/iovs.12-9712.

Abstract

Purpose: To study sequential changes in retinal ganglion cell (RGC) morphology in mice after optic nerve crush and after induction of experimental glaucoma.

Methods: Nerve crush or experimental glaucoma was induced in mice that selectively express yellow fluorescent protein (YFP) in RGCs. Mice were euthanized 1, 4, and 9 days after crush and 1, 3, and 6 weeks after induction of glaucoma by bead injection. All YFP-RGCs were identified in retinal whole mounts. Then confocal images of randomly selected RGCs were quantified for somal fluorescence brightness, soma size, neurite outgrowth, and dendritic complexity (Sholl analysis).

Results: By 9 days after crush, 98% of RGC axons died and YFP-RGCs decreased by 64%. After 6 weeks of glaucoma, 31% of axons died, but there was no loss of YFP-RGC bodies. All crush retinas combined had significant decreases in neurite outgrowth parameters (P ≤ 0.036, generalized estimating equation [GEE] model) and dendritic complexity was lower than controls (P = 0.017, GEE model). There was no change in RGC soma area after crush. In combined glaucoma data, the RGC soma area was larger than control (P = 0.04, GEE model). At 3 weeks, glaucoma RGCs had significantly larger values for dendritic structure and complexity than controls (P = 0.044, GEE model), but no statistical difference was found at 6 weeks.

Conclusions: After nerve crush, RGCs and axons died rapidly, and dendritic structure decreased moderately in remaining RGCs. Glaucoma caused an increase in RGC dendrite structure and soma size at 3 weeks.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis*
  • Axons / pathology*
  • Bacterial Proteins / metabolism
  • Disease Models, Animal*
  • Female
  • Fluorescent Dyes / metabolism
  • Glaucoma / metabolism
  • Glaucoma / pathology*
  • Intraocular Pressure
  • Luminescent Proteins / metabolism
  • Male
  • Mice
  • Microscopy, Confocal
  • Nerve Crush
  • Optic Nerve Injuries / metabolism
  • Optic Nerve Injuries / pathology*
  • Retinal Ganglion Cells / metabolism
  • Retinal Ganglion Cells / pathology*

Substances

  • Bacterial Proteins
  • Fluorescent Dyes
  • Luminescent Proteins
  • yellow fluorescent protein, Bacteria