Interrelationship between retinal ischaemic damage and turnover and metabolism of putative amino acid neurotransmitters, glutamate and GABA Article DOI:
Cite this article as: Robin, L.N. & Kalloniatis, M. Doc Ophthalmol (1992) 80: 273. doi:10.1007/BF00154376 Abstract
Conditions causing a reduction of oxygen availability (anoxia), such as stroke or diabetes, result in drastic changes in ion movements, levels of neurotransmitters and metabolites and subsequent neural death. Currently, there is no clinically available treatment for anoxia induced neural cell death resulting in drastic and permanent central nervous system dysfunction. However, there have been some exciting developments in experimentally induced anoxic conditions where several classes of drugs appear to significantly reduce neural cell death. This report aims to provide the foundations for understanding both the basic mechanisms involved in retinal ischaemic damage and experimental treatments used to prevent such damage. We discuss the normal release, actions and uptake of the fast retinal neurotransmitters, glutamate and GABA, in the vertebrate retina. Immunocytochemistry is used to demonstrate that both glutamate and GABA are found in the macaque retina. Following this is a discussion on how ischaemia may enhance neurotransmitter release or disrupt its uptake, thus causing an increase in extracellular concentration of these neurotransmitters and subsequent neuronal damage. The mechanisms involved in glutamate neurotoxicity are reviewed, because excess glutamate is the likely cause of retinal ischaemic damage. Finally, the mechanisms behind four possible modes of treatment of neurotransmitter toxicity and their advantages and disadvantages are discussed. Hopefully, further research in this area will lead to the development of a rational therapy for retinal, as well as cerebral ischaemia.
Key words Anoxia GABA glutamate immunocytochemistry ischaemia neurotransmitters retina Abbreviations α-KG
aspartate amino transferase
amacrine cell layer
central nervous system
excitatory amino acids
γ-amino butyric acid
glumatic acid decarboxylase
ganglion cell layer
inner limiting membrane
inner nuclear layer
inner plexiform layer
inner segment of photoreceptor
nerve fibre layer
outer limiting membrane
outer nuclear layer
outer plexiform layer
outer segment of photoreceptor
succinate semi-aldehyde decarboxylase
succinate semi aldehyde
tricarboxylic acid cycle
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