Quantification of amino acid neurochemistry secondary to NMDA or betaxolol application.
BACKGROUND
Alterations in retinal amino acid neurochemistry are an indicator of metabolic function. Glutamate is the primary excitatory amino acid neurotransmitter within the retina, and excessive levels of glutamate can potentially cause excitotoxicity, in particular, through the N-methyl-D-aspartate (NMDA) subtype of glutamate receptor. Anomalies in NMDA receptor function have been implicated as causing many neurodegenerative disorders, and overactivation leads to neuronal death secondary to metabolic insult. Several pharmaceutical agents have been proposed as potential neuroprotective agents against excitotoxicity (e.g. betaxolol), yet any effects such drugs have on retinal neurochemistry have not been determined. Therefore, the aim of this study was to quantify the changes in retinal amino acid neurochemistry secondary to the application of NMDA with and without betaxolol.


METHODS
Functional NMDA channel activation was confirmed in both amacrine and ganglion cells by quantifying the entry into these neurones of a channel permeable probe (agmatine: 1-amino-4-guanidobutane [AGB]). By probing serial thin sections with immunoglobulins targeting AGB, glutamate, gamma-aminobutyric acid (GABA) and glycine, it was possible to simultaneously study the neurochemical characteristic as well as the NMDA-evoked AGB responses of different neurochemical populations of inner retinal neurones.


RESULTS
The authors have previously shown no accumulation of glutamate or GABA within Muller cells following NMDA application. Herein they report altered GABA and glycine immunoreactivity, but not glutamate immunoreactivity within neurones of the amacrine and ganglion cell layers following NMDA application. Finally, the addition of betaxolol did not significantly alter the normal neurochemistry of the retina.


CONCLUSIONS
The retina possesses intrinsic mechanisms that allow it to maintain metabolic integrity during short periods of high NMDA application.
Sun
Daniel
D
Department of Optometry, University of Auckland, Auckland, New Zealand.
Kalloniatis
Michael
M
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000376:Agmatine / Q000378:metabolism; D025042:Amacrine Cells / Q000166:cytology / Q000378:metabolism; D000818:Animals; D015784:Betaxolol / Q000494:pharmacology*; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000378:metabolism*; D005998:Glycine / Q000378:metabolism*; D007150:Immunohistochemistry; D016202:N-Methylaspartate / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D011817:Rabbits; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D012160:Retina / Q000187:drug effects* / Q000378:metabolism; D012165:Retinal Ganglion Cells / Q000166:cytology / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D000319:Adrenergic beta-Antagonists; D018690:Excitatory Amino Acid Agonists; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D016202:N-Methylaspartate; D000376:Agmatine; D015784:Betaxolol; D005998:Glycine