September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
Upregulation of Retinal Glutamate in Chronic Experimental Glaucoma
Author Affiliations & Notes
  • T Michael Nork
    Ophthalmology and Visual Sciences, University of Wisconsin--Madison, Madison, Wisconsin, United States
    OSOD (Ocular Services On Demand), LLC, Madison, Wisconsin, United States
  • Hau Nguyen
    Ophthalmology and Visual Sciences, University of Wisconsin--Madison, Madison, Wisconsin, United States
  • Alexander Katz
    Ophthalmology and Visual Sciences, University of Wisconsin--Madison, Madison, Wisconsin, United States
  • Ying Ge
    Cell and Regenerative Biology, University of Wisconsin--Madison, Madison, Wisconsin, United States
  • Charlene B Y Kim
    Ophthalmology and Visual Sciences, University of Wisconsin--Madison, Madison, Wisconsin, United States
    OSOD (Ocular Services On Demand), LLC, Madison, Wisconsin, United States
  • Vijaykrishna Raghunathan
    Surgical and Radiological Sciences, University of California, Davis, Davis, California, United States
  • Paul Russell
    Surgical and Radiological Sciences, University of California, Davis, Davis, California, United States
  • Paul Miller
    Surgical Sciences, University of Wisconsin--Madison, Madison, Wisconsin, United States
    OSOD (Ocular Services On Demand), LLC, Madison, Wisconsin, United States
  • Christopher J Murphy
    Ophthalmology and Vision Science, School of Medicine, University of California, Davis, Davis, California, United States
    OSOD (Ocular Services On Demand), LLC, Madison, Wisconsin, United States
  • Brian J Christian
    Toxicology, Covance, Madison, Wisconsin, United States
  • Footnotes
    Commercial Relationships   T Michael Nork, None; Hau Nguyen, None; Alexander Katz, None; Ying Ge, None; Charlene Kim, None; Vijaykrishna Raghunathan, None; Paul Russell, None; Paul Miller, None; Christopher Murphy, None; Brian Christian, None
  • Footnotes
    Support  NIH (NEI) P30 EY016665, Research to Prevent Blindness, Covance Inc., OSOD (Ocular Services On Demand) LLC
Investigative Ophthalmology & Visual Science September 2016, Vol.57, 2573. doi:
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    • Get Citation

      T Michael Nork, Hau Nguyen, Alexander Katz, Ying Ge, Charlene B Y Kim, Vijaykrishna Raghunathan, Paul Russell, Paul Miller, Christopher J Murphy, Brian J Christian; Upregulation of Retinal Glutamate in Chronic Experimental Glaucoma. Invest. Ophthalmol. Vis. Sci. 2016;57(12):2573.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : The role, if any, of glutamate excitotoxicity in glaucoma is controversial. Previous attempts at measuring vitreous glutamate levels in both human and chronic experimental glaucoma (ExGl) in macaques have yielded contradictory results. Here, we investigate the local modulation of glutamate levels within the retina.

Methods : Ten macaques underwent laser trabecular destruction in the right eye. The intraocular pressures were elevated to above 25 mmHg for from 1 to 8 years. Six of the animals underwent bilateral enucleation at the time of euthanasia. The anterior segments were promptly removed and two 6 mm punches were removed from each retina—one from the superior and one from the inferior arcuate region. The removed tissue was then flash frozen in liquid nitrogen. Levels of free glutamate and taurine were then determined by mass spectrometry (MS). The remaining 4 macaques underwent perfusion fixation with glutaraldehyde. Segments of retina in the perimacular region were removed, embedded in epon and underwent immunohistochemical (IHC) staining for glutamate.

Results : MS showed no statistically significant difference in glutamate levels between the control and ExGl eyes. However, IHC revealed marked upregulation in glutamate staining in all 4 of the perfusion fixed ExGl eyes at the level of the rod spherules and cone pedicles. There was also increased glutamate staining in the inner plexiform layer. The retinal ganglion cell (RGC) and nerve fiber (NF) layers were nearly absent in the ExGl eyes.

Conclusions : The apparently contradictory MS and IHC results may be because the ExGl retinas are much thinner than the controls—missing their RGC and NF layers, which normally contain glutamate. Glutamate upregulation on IHC was present mostly in the rod spherules and cone pedicles (perhaps due to photoreceptor ischemia). These findings could explain the results of previous studies that failed to consistently show elevated glutamate levels in the vitreous. Furthermore, upregulation of glutamate at the critical photoreceptor and possibly bipolar synapses leaves open the possibility that excitotoxicity contributes to RGC injury in glaucoma.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.

 

IHC for glutamate in the control retina. Arrows show rod spherules and cone pedicles.

IHC for glutamate in the control retina. Arrows show rod spherules and cone pedicles.

 

IHC for glutamate in the ExGl fellow eye. There is markedly increased staining in the rod spherules and cones pedicles (arrows).

IHC for glutamate in the ExGl fellow eye. There is markedly increased staining in the rod spherules and cones pedicles (arrows).

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