Retinal ganglion cell morphology after optic nerve crush and experimental glaucoma

Giedrius Kalesnykas, Ericka N. Oglesby, Donald J Zack, Frances E. Cone, Matthew R. Steinhart, Jing Tian, Mary Ellen Pease, Harry A Quigley

Research output: Contribution to journalArticle

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 YFPRGCs 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.

Original languageEnglish (US)
Pages (from-to)3847-3857
Number of pages11
JournalInvestigative Ophthalmology and Visual Science
Volume53
Issue number7
DOIs
StatePublished - Jun 2012

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Nerve Crush
Retinal Ganglion Cells
Optic Nerve
Glaucoma
Carisoprodol
Axons
Proteins
Statistical Models
Dendrites
Systems Analysis
Retina
Fluorescence
Injections

ASJC Scopus subject areas

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

Cite this

Retinal ganglion cell morphology after optic nerve crush and experimental glaucoma. / Kalesnykas, Giedrius; Oglesby, Ericka N.; Zack, Donald J; Cone, Frances E.; Steinhart, Matthew R.; Tian, Jing; Pease, Mary Ellen; Quigley, Harry A.

In: Investigative Ophthalmology and Visual Science, Vol. 53, No. 7, 06.2012, p. 3847-3857.

Research output: Contribution to journalArticle

Kalesnykas, Giedrius ; Oglesby, Ericka N. ; Zack, Donald J ; Cone, Frances E. ; Steinhart, Matthew R. ; Tian, Jing ; Pease, Mary Ellen ; Quigley, Harry A. / Retinal ganglion cell morphology after optic nerve crush and experimental glaucoma. In: Investigative Ophthalmology and Visual Science. 2012 ; Vol. 53, No. 7. pp. 3847-3857.
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AU - Tian, Jing

AU - Pease, Mary Ellen

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N2 - 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 YFPRGCs 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.

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