Lack of neuroprotection against experimental glaucoma in c-Jun N-terminal kinase 3 knockout mice

Harry A. Quigley, Frances E. Cone, Scott E. Gelman, Zhiyong Yang, Janice L. Son, Ericka N. Oglesby, Mary E. Pease, Donald J. Zack

Research output: Contribution to journalArticle

Abstract

To determine if the absence of c-Jun N-terminal kinase 3 (JNK3) in the mouse retina would reduce retinal ganglion cell (RGC) loss in mice with experimental glaucoma. C57BL/6 mice underwent experimental intraocular pressure (IOP) elevation with a bead/viscoelastic injection into one eye. One-half of the mice were Jnk3 homozygous knockouts (KO) and were compared to wild type (WT) mice. IOP was measured under anesthesia with the TonoLab, axial length was measured post-mortem with calipers after inflation to 15mmHg, and RGC layer counts were performed on retinal whole mount images stained with DAPI, imaged by confocal microscopy, and counted by masked observers in an image analysis system. Axon counts were performed in optic nerve cross-sections by semi-automated image analysis. Both WT and Jnk3-/- mice had mean elevations of IOP of more than 50% after bead injection. Both groups underwent the expected axial globe elongation due to chronic IOP elevation. The absence of JNK3 in KO retina was demonstrated by Western blots. RGC layer neuron counts showed modest loss in both WT and Jnk3-/- animals; local differences by retinal eccentricity were detected, in each case indicating greater loss in KO animals than in WT. The baseline number of RGC layer cells in KO animals was 10% higher than in WT, but the number of optic nerve axons was identical in KO and WT controls. A slightly greater loss of RGC in Jnk3-/- mice compared to controls was detected in experimental mouse glaucoma by RGC layer counting and there was no protective effect shown in axon counts. Counts of RGC layer cells and optic nerve axons indicate that Jnk3-/- mice have an increased number of amacrine cells compared to WT controls.

Original languageEnglish (US)
Pages (from-to)299-305
Number of pages7
JournalExperimental eye research
Volume92
Issue number4
DOIs
StatePublished - Apr 1 2011

Keywords

  • C-Jun N-terminal kinase
  • Glaucoma
  • Neuroprotection
  • Pathogenesis
  • Retinal ganglion cell

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

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