Hof P R, Lee P Y, Yeung G, Wang R F, Podos S M, Morrison J H
Neurobiology of Aging Laboratories, Mount Sinai School of Medicine, New York, New York, 10029, USA.
Exp Neurol. 1998 Oct;153(2):234-41. doi: 10.1006/exnr.1998.6881.
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 NMDAR1-immunoreactive ganglion cells were dramatically reduced compared to unaffected fellow eyes, but GluR2- 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.
兴奋性氨基酸神经毒性已被提出是青光眼选择性神经元死亡的潜在机制。在猕猴实验性青光眼中，通过用氩激光或二极管激光烧灼一只眼的小梁网来研究谷氨酸受体亚基蛋白GluR2和NMDAR1的细胞分布与特定视网膜神经元亚群易损性之间的关系。使用针对GluR2和NMDAR1亚基蛋白以及神经丝蛋白的特异性单克隆抗体对视网膜节段进行免疫染色。对视网膜中免疫反应性的分布进行定性评估，并对每个视网膜节段的中央旁和周边区域的神经节细胞进行计数。在对照眼中，这两种谷氨酸受体亚基蛋白的免疫反应性广泛分布于大多数视网膜神经元类型中，并与神经节细胞中的神经丝蛋白共定位。在青光眼眼中，与未受影响的对侧眼相比，GluR2和NMDAR1免疫反应性神经节细胞的密度显著降低，但水平细胞、双极细胞和无长突细胞的GluR2和NMDAR1免疫反应性群体未受影响。这些数据与先前在该青光眼实验模型中关于神经节细胞选择性易损性的观察结果一致。然而，GluR2和NMDAR1亚基并不构成青光眼中易损性的细胞类型特异性标志物，因为它们存在于易发生变性的神经元以及抗性神经元中。虽然青光眼的视网膜病理涉及可能与调节钙通量的谷氨酸受体亚基相关的兴奋毒性机制，但神经元易损性的特定模式显然取决于其他细胞特征，如形态、连接性和神经化学表型的其他方面。
