Retinal ganglion cell loss in a rat ocular hypertension model is sectorial and involves early optic nerve axon loss

Ileana Soto, Mary E. Pease, Janice L. Son, Xiaohai Shi, Harry A. Quigley, Nicholas Marsh-Armstrong

Research output: Contribution to journalArticle

68 Scopus citations

Abstract

PURPOSE. Previous analyses of the DBA/2J mouse glaucoma model show a sectorial degeneration pattern suggestive of an optic nerve head insult. In addition, there are large numbers of retinal ganglion cells (RGCs) that cannot be retrogradely labeled but maintain RGC gene expression, and many of these have somatic phosphorylated neurofilament labeling. Here the authors further elucidate these features of glaucomatous degeneration in a rat ocular hypertension model. METHODS. IOP was elevated in Wistar rats by translimbal laser photocoagulation. Retina whole mounts were analyzed for Sncg mRNA in situ hybridization, fluorogold (FG) retrograde labeling, and immunohistochemistry for phosphorylated neurofilaments (pNF) at 10 and 29 days after IOP increase. A novel automatic method was used to estimate axon numbers in plastic sections of optic nerves. RESULTS. Sncg mRNA was confirmed as a specific marker for RGCs in rat. Loss of RGCs after IOP elevation occurred in sectorial patterns. Sectors amid degeneration contained RGCs that were likely disconnected because these had pNF in their somas and dendrites, were not labeled by FG, and were associated with reactive plasticity within the retina. Most of the axon loss within the optic nerve already occurred by 10 days after the onset of IOP elevation. CONCLUSIONS. These data demonstrate that the pattern of RGC loss after laser-induced ocular hypertension in rats is similar to that previously reported in DBA/2J mice. The results support the view that in glaucoma RGC axons are damaged at the optic nerve head and degenerate within the optic nerve before there is loss of RGC somas.

Original languageEnglish (US)
Pages (from-to)434-441
Number of pages8
JournalInvestigative Ophthalmology and Visual Science
Volume52
Issue number1
DOIs
StatePublished - Jan 1 2011
Externally publishedYes

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience
  • Medicine(all)

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