The Monkey as a Model in Methanol Poisoning

Martin-Amat, G.; McMartin, Kenneth E.; Makar, A B; Baumbach, Gary L.; Cancilla, Pasquale A.; Hayreh, M.M.; Hayreh, S S; Tephly, Thomas R.

doi:10.1016/b978-0-12-691402-3.50044-5

Cited by 3 publications

(4 citation statements)

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“…Formic acid is the toxic metabolite responsible for the retinal and optic nerve toxicity produced in methanol intoxication (5,8,12,15). Linear increases in blood formate concentrations were observed in both methanolintoxicated and LED-treated, methanol-intoxicated rats during the 72-h intoxication period (Fig.…”

Section: Blood Formate Accumulation In Methanol-intoxicated Rats Is Notmentioning

confidence: 99%

“…Decrements in mitochondrial function have also been postulated to be involved in the pathogenesis in methanol intoxication (4)(5)(6)(7). Methanol intoxication produces toxic injury to the retina and optic nerve, frequently resulting in blindness.…”

mentioning

confidence: 99%

“…Formic acid is the toxic metabolite responsible for the retinal and optic nerve toxicity produced in methanol intoxication (4)(5)(6)(7)15). Formic acid is a mitochondrial toxin that inhibits cytochrome c oxidase, the terminal enzyme of the mitochondrial electron transport chain of all eukaryotes (16,17).…”

mentioning

confidence: 99%

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Therapeutic photobiomodulation for methanol-induced retinal toxicity

Eells

Henry

Summerfelt

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

350

264

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Methanol intoxication produces toxic injury to the retina and optic nerve, resulting in blindness. The toxic metabolite in methanol intoxication is formic acid, a mitochondrial toxin known to inhibit the essential mitochondrial enzyme, cytochrome oxidase. Photobiomodulation by red to near-IR radiation has been demonstrated to enhance mitochondrial activity and promote cell survival in vitro by stimulation of cytochrome oxidase activity. The present studies were undertaken to test the hypothesis that exposure to monochromatic red radiation from light-emitting diode (LED) arrays would protect the retina against the toxic actions of methanolderived formic acid in a rodent model of methanol toxicity. Using the electroretinogram as a sensitive indicator of retinal function, we demonstrated that three brief (2 min, 24 s) 670-nm LED treatments (4 J͞cm 2 ), delivered at 5, 25, and 50 h of methanol intoxication, attenuated the retinotoxic effects of methanolderived formate. Our studies document a significant recovery of rod-and cone-mediated function in LED-treated, methanol-intoxicated rats. We further show that LED treatment protected the retina from the histopathologic changes induced by methanolderived formate. These findings provide a link between the actions of monochromatic red to near-IR light on mitochondrial oxidative metabolism in vitro and retinoprotection in vivo. They also suggest that photobiomodulation may enhance recovery from retinal injury and other ocular diseases in which mitochondrial dysfunction is postulated to play a role. D ecrements in mitochondrial function have been postulated to be involved in the pathogenesis of numerous retinal and optic nerve diseases, including age-related macular degeneration, diabetic retinopathy, and Leber's hereditary optic neuropathy (1-3). Decrements in mitochondrial function have also been postulated to be involved in the pathogenesis in methanol intoxication (4-7). Methanol intoxication produces toxic injury to the retina and optic nerve, frequently resulting in blindness. A toxic exposure to methanol typically results in the development of formic acidemia, metabolic acidosis, visual toxicity, coma, and, in extreme cases, death (8, 9). Visual disturbances generally develop between 18 and 48 h after methanol ingestion and range from misty or blurred vision to complete blindness. Both acute and chronic methanol exposure have been shown to produce retinal dysfunction and optic nerve damage clinically (8-10) and in experimental animal models (11)(12)(13)(14).Formic acid is the toxic metabolite responsible for the retinal and optic nerve toxicity produced in methanol intoxication (4-7, 15). Formic acid is a mitochondrial toxin that inhibits cytochrome c oxidase, the terminal enzyme of the mitochondrial electron transport chain of all eukaryotes (16,17). Cytochrome oxidase is an important energy-generating enzyme critical for the proper functioning of almost all cells, especially those of highly oxidative organs, including the retina and brain (18). Previous studies in...

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Section: Blood Formate Accumulation In Methanol-intoxicated Rats Is Notmentioning

confidence: 99%

mentioning

confidence: 99%

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Therapeutic photobiomodulation for methanol-induced retinal toxicity

Eells

Henry

Summerfelt

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

350

264

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“…Edema of the disc is reported in monkeys with methyl alcohol poisoning (35) and trimethyltin acetate (36). Salicylanilide (37) causes vacuolation of the cerebral white matter in the dog and edema of the disc (Fig.…”

Section: April 1982mentioning

confidence: 99%

Histopathological and Laboratory Assessment of Visual Dysfunction

Heywood¹

1982

Environmental Health Perspectives

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The currently available methods of assessing ocular toxicity are discussed. Manifestations of ocular toxicity are best described clinically; histopathological examination of the eye is beset with problems of preparing the eye for morphological examination. Electron microscopy is essential to look for chemically induced side effects at the cellular level. Mechanisms of ocular toxicity are poorly understood, and the limitation of animal studies in predicting side effects in man must be appreciated.

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