[Cellular and molecular biology of ischemic retina].
We introduce our studies on the retinal ischemia in light of both pre- and post-Noell viewpoints. For several years now, we have employed in vivo intraretinal microelectrodes for this field of experiments. This series of studies on the cat eye revealed that the sensory retina as well as the retinal pigment epithelium is severely damaged after only a ten-minute stoppage of blood flow. This phenomenon in usually masked in the routine electroretinogram, a mass electrical response of the retina monitored from the ocular surface. Our studies, employing cultured amacrine cells from embryonic rat eyes, revealed that ischemic changes in neural cells are induced by an increase in extracellular glutamate. Among the glutamate analogs, N-methyl-D-aspartate (NMDA) is responsive to this change. An influx of calcium through NMDA receptor channels activates nitric oxide synthase (NOS), inducing intracellular nitric oxide (NO) in selected amacrine cells. Nitric oxide reacts with free radicals in the cell and induces peroxinitrite, which is toxic. This cascade triggered by ischemia is interrupted by extracellular zinc, magnesium, hemoglobin, nitroprusside, s-nitrosocysteine, and some NMDA antagonists. In terms of clinical application, there is a possibility that dihydroxyphenylalanine (DOPA), superoxide dismutase (SOD), and catalase (CAT), as well as vitamins B6 and B12, are important candidates for administration before an ischemic attack for prevention of damage to the retinal neurons. Gene expression of NOS, interleukin (IL)-1, IL-6, tumor necrosing factor (TNF), and transforming growth factor (TGF)-beta in the ischemic retina was investigated in order to discover reaction substances common to ischemic change and inflammation.
Honda
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Department of Ophthalmology and Visual Sciences Graduate School of Medicine, Kyoto University.
D000818:Animals; D017209:Apoptosis; D002415:Cats; D016923:Cell Death; D016207:Cytokines / Q000235:genetics; D018846:Excitatory Amino Acids / Q000633:toxicity; D007511:Ischemia / Q000378:metabolism; D009569:Nitric Oxide / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000378:metabolism; D010101:Oxygen Consumption; D051381:Rats; D012160:Retina / Q000378:metabolism / Q000473:pathology; D012171:Retinal Vessels / Q000378:metabolism / Q000473:pathology*
D016207:Cytokines; D018846:Excitatory Amino Acids; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase