A Rat Model Manifesting Methanol-Induced Visual Dysfunction Suitable for Both Acute and Long-Term Exposure Studies

Lee, Eun Woo; Garner, Charles D.; Terzo, Thomas S.

doi:10.1006/taap.1994.1198

Cited by 26 publications

(13 citation statements)

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“…In these ani- mal models, formate oxidation has been selectively inhibited by dietary (Lee, et al, 1994) or chemical (Eells et al, 1981) depletion of folate coenzymes, thus allowing formate to accumulate to toxic concentrations following methanol administration. Methanol-intoxicated rats developed formic acidemia, metabolic acidosis, and visual toxicity analogous to the human methanol poisoning syndrome (Eells, 1991;Murray et al, 1991;Lee et al, 1994). Visual dysfunction was measured as reductions in the flash-evoked cortical potential (FEP) and electroretinogram (ERG).…”

Section: Disruption Of Retinal Mitochondrial Function By Formate In Mmentioning

confidence: 99%

Mitochondria-Mediated Cell Injury

et al. 1997

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Section: Disruption Of Retinal Mitochondrial Function By Formate In Mmentioning

confidence: 99%

Mitochondria-Mediated Cell Injury

et al. 1997

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“…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).…”

mentioning

confidence: 99%

mentioning

confidence: 99%

Therapeutic photobiomodulation for methanol-induced retinal toxicity

Eells

Henry

Summerfelt

et al. 2003

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

345

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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“…The mammalian retinas are highly susceptible to chemical compounds, and various toxicants are known to cause retinal degeneration (Lee et al, 1994;Ferreira et al, 1998;Eells et al, 1996;Rai et al, 2013;Mela et al, 2012;Singalavanija et al, 2000). Among these toxicants, MNU is a direct-acting alkylating agent that induces selective PR death via apoptosis mechanism in various mammalian eyes (Petrin et al, 2003;Yoshizawa et al, 2009;Kidney and Faustman, 1995).…”

Section: Discussionmentioning

confidence: 97%