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Molecular Architecture of Glutamate Signaling Pathway in Glaucomatous Optic Neuropathy

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Neuroprotection and Neuroregeneration for Retinal Diseases

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Abstract

Glutamate is the predominant excitatory neurotransmitter in the central nervous system. Excessive concentrations of glutamate have been reported in various neurological diseases, including glaucomatous optic neuropathy (GON). Glutamate excitotoxicity triggered by overstimulation of N-methyl-d-aspartate (NMDA)-type glutamate receptors may contribute to retinal ganglion cell (RGC) degeneration in glaucoma and other retinal neuronal cell death in ischemic insult including diabetic retinopathy. Neuroprotective effects with the blockage of overstimulated NMDA receptors were found in several previous studies in RGC degeneration models, such as the axotomy, ischemia, and laser-induced high intraocular pressure models. Although there is a great deal of evidence for elevated glutamate in GON, a clinical trial of memantine, an NMDA receptor antagonist, was unsuccessful. Thus, excitotoxicity is not recognized as a primary factor in GON, although glutamate leaking from dying/dead RGCs or compromised glia may contribute to the secondary death of neighboring RGCs via excessive activation of NMDA receptors during the development of glaucoma. Therefore, appropriate modulation of NMDA receptor-mediated retinal excitotoxicity remains to be elucidated and may become a possible therapeutic target.

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Authors and Affiliations

  1. Department of Ophthalmology, St. Marianna University School of Medicine, 2-16-1 Sugao, Miyamae, Kawasaki, 216-8511, Japan

    Yasunari Munemasa

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  1. Yasunari Munemasa
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Correspondence to Yasunari Munemasa .

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Editors and Affiliations

  1. Department of Ophthalmology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan

    Toru Nakazawa

  2. Department of Ophthalmology, St. Marianna University School of Medicine, Kawasaki, Japan

    Yasushi Kitaoka

  3. Visual Research Project, Tokyo Metropolitan Inst of Med Sci, Tokyo, Japan

    Takayuki Harada

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Munemasa, Y. (2014). Molecular Architecture of Glutamate Signaling Pathway in Glaucomatous Optic Neuropathy. In: Nakazawa, T., Kitaoka, Y., Harada, T. (eds) Neuroprotection and Neuroregeneration for Retinal Diseases. Springer, Tokyo. https://doi.org/10.1007/978-4-431-54965-9_1

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