GLUTAMATE-RECEPTOR SUBUNIT GLUR2 AND NMDAR1 IMMUNOREACTIVITY IN THE RETINA OF MACAQUE MONKEYS WITH EXPERIMENTAL GLAUCOMA DOES NOT IDENTIFY VULNERABLE NEURONS

Excitatory amino acid neurotoxicity has been proposed as a mechanism u nderlying selective neuronal death in glaucoma. The relationships betw een the cellular distribution of glutamate receptor subunit proteins G luR2 and NMDAR1 and the vulnerability of restricted retinal neuron sub populations 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 us ing specific monoclonal antibodies to the GluR2 and NMDAR1 subunit pro teins as well as neurofilament protein. The distribution of immunoreac tivity was qualitatively assessed in the retina, and ganglion cells we re counted in the paracentral and peripheral regions of each retinal s egment. Immunoreactivity for both of these glutamate receptor subunit proteins was widely distributed in most retinal neuron types in contro l eyes and was colocalized with neurofilament protein in ganglion cell s. in the glaucomatous eyes, densities of GluR2- and NMDAR1-immunoreac tive ganglion cells were dramatically reduced compared to unaffected f ellow eyes, but GluR2- and NMDAR1-immunoreactive populations of horizo ntal, bipolar, and amacrine cells were not affected. These data parall el previous observations on the selective vulnerability of ganglion ce lls 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 w eb as in resistant ones. While retinal pathology in glaucoma involves excitotoxic mechanisms that may be related to glutamate receptor subun its regulating calcium fluxes, the specific pattern of neuronal vulner ability clearly depends on other cellular characteristics such as morp hology, connectivity, and other aspects of the neurochemical phenotype . (C) 1998 Academic Press.