Regulation of excitatory amino acid transmission in the retina

Studies on neuroprotection

Catherine A. Opere, Segewkal Heruye, Ya Fatou Njie-Mbye, Sunny E. Ohia, Najam A. Sharif

Research output: Contribution to journalArticle

Abstract

Excitotoxicity occurs in neurons due to the accumulation of excitatory amino acids such as glutamate in the synaptic and extrasynaptic locations. In the retina, excessive glutamate concentrations trigger a neurotoxic cascade involving several mechanisms, including the elevation of intracellular calcium (Ca2+) and the activation of α-amino-3-hydroxy 5-methyl-4-iso-xazole-propionic acid/kainate (AMPA/KA) and N-methyl-d-aspartate (NMDA) receptors leading to retinal degeneration. Both ionotropic glutamate receptors (iGluRs) and metabotropic glutamate receptors (mGluRs) are present in the mammalian retina. Indeed, due to the abundant expression of GluRs, the mammalian retina is highly susceptible to excitotoxic neurodegeneration. Excitotoxicity has been postulated to present a common downstream mechanism for several stimuli, including hypoglycemia, hypoxia, ischemia, and chronic neurodegenerative diseases. Experimental approaches to the study of neuroprotection in the retina have utilized insults that trigger hypoxia, hypoglycemia, or excitotoxicity. Using these experimental approaches, the neuroprotective potential of GluR agents, including the NMDA receptor modulators (MK801, ifenprodil, memantine); AMPA/KA receptor antagonist (CNQX); Group II and III mGluR agonists (LY354740, quisqualate); and Ca2+-channel blockers (diltiazem, lomerizine, verapamil, ω-conotoxin), and others (pituitary adenylate cyclase activating polypeptide, neuropeptide Y, acetylcholine receptor agonists) have been elucidated. In addition to corroborating the exocytotic role of excitatory amino acids in retinal degeneration, these studies affirm that multiple mechanism/s contribute to the prevention of damage caused by excitotoxicity in the retina. Therefore, it is feasible that several pathways are involved in protecting the retina from toxic insults in ocular neurodegenerative conditions such as glaucoma and retinal ischemia. Furthermore, these experimental models are viable tools for evaluating therapeutic candidates in ocular neuropathies.

Original languageEnglish (US)
Pages (from-to)107-118
Number of pages12
JournalJournal of Ocular Pharmacology and Therapeutics
Volume34
Issue number1-2
DOIs
StatePublished - Jan 1 2018

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Excitatory Amino Acids
Retina
Retinal Degeneration
Hypoglycemia
eglumetad
Glutamic Acid
Ischemia
Conotoxins
Neuropeptide Y Receptors
Quisqualic Acid
Memantine
6-Cyano-7-nitroquinoxaline-2,3-dione
Pituitary Adenylate Cyclase-Activating Polypeptide
Ionotropic Glutamate Receptors
Kainic Acid Receptors
Cholinergic Agonists
Metabotropic Glutamate Receptors
Diltiazem
Kainic Acid
Poisons

All Science Journal Classification (ASJC) codes

  • Ophthalmology
  • Pharmacology
  • Pharmacology (medical)

Cite this

Regulation of excitatory amino acid transmission in the retina : Studies on neuroprotection. / Opere, Catherine A.; Heruye, Segewkal; Njie-Mbye, Ya Fatou; Ohia, Sunny E.; Sharif, Najam A.

In: Journal of Ocular Pharmacology and Therapeutics, Vol. 34, No. 1-2, 01.01.2018, p. 107-118.

Research output: Contribution to journalArticle

Opere, Catherine A. ; Heruye, Segewkal ; Njie-Mbye, Ya Fatou ; Ohia, Sunny E. ; Sharif, Najam A. / Regulation of excitatory amino acid transmission in the retina : Studies on neuroprotection. In: Journal of Ocular Pharmacology and Therapeutics. 2018 ; Vol. 34, No. 1-2. pp. 107-118.
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