Glutamate receptor subunit GluR2 and NMDAR1 immunoreactivity in the retina of macaque monkeys with experimental glaucoma does not identify vulnerable neurons

Patrick R. Hof, Ping Yu Lee, Glendy Yeung, Rong Fang Wang, Steven M. Podos, John Morrison

Research output: Contribution to journalArticle

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Abstract

Excitatory amino acid neurotoxicity has been proposed as a mechanism underlying selective neuronal death in glaucoma. The relationships between the cellular distribution of glutamate receptor subunit proteins GluR2 and NMDAR1 and the vulnerability of restricted retinal neuron subpopulations was explored in experimental glaucoma in macaque monkeys, produced by treating the trabecular meshwork in one eye with argon or diode laser burns. Immunostaining of retinal segments was performed using specific monoclonal antibodies to the GluR2 and NMDAR1 subunit proteins as well as neurofilament protein. The distribution of immunoreactivity was qualitatively assessed in the retina, and ganglion cells were counted in the paracentral and peripheral regions of each retinal segment. Immunoreactivity for both of these glutamate receptor subunit proteins was widely distributed in most retinal neuron types in control eyes and was colocalized with neurofilament protein in ganglion cells. In the glaucomatous eyes, densities of GluR2- and NMDARl- immunoreactive ganglion cells were dramatically reduced compared to unaffected fellow eyes, but GIuR2- and NMDAR1-immunoreactive populations of horizontal, bipolar, and amacrine cells were not affected. These data parallel previous observations on the selective vulnerability of ganglion cells in this experimental model of glaucoma. However, GluR2 and NMDAR1 subunits do not constitute cell type-specific markers of vulnerability in glaucoma as they are present in neurons prone to degeneration as well as in resistant ones. While retinal pathology in glaucoma involves excitotoxic mechanisms that may be related to glutamate receptor subunits regulating calcium fluxes, the specific pattern of neuronal vulnerability clearly depends on other cellular characteristics such as morphology, connectivity, and other aspects of the neurochemical phenotype.

Original languageEnglish (US)
Pages (from-to)234-241
Number of pages8
JournalExperimental Neurology
Volume153
Issue number2
DOIs
StatePublished - Jan 1 1998
Externally publishedYes

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Keywords

  • Excitotoxicity
  • Experimental glaucoma
  • Ganglion cells
  • Glutamate receptors
  • Retina
  • Selective vulnerability

ASJC Scopus subject areas

  • Neurology
  • Developmental Neuroscience

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