Müller cell involvement in methanol-induced retinal toxicity.
Methanol is an ocular toxicant which causes visual dysfunction often leading to blindness after acute exposure. The physiological and biochemical changes responsible for this toxicity are poorly understood. Previously, we reported that the folate-reduced (FR) rat is an animal model which mimics the characteristic human methanol toxicities. The present study examines the hypothesis that depletion of ATP after methanol administration is the initiating event in methanol-induced retinal toxicity. ATP is reduced in retinae of methanol-treated FR rats to the same extent as is seen in retinae of FR and folate-sufficient (FS) rats treated with the Müller cell (retinal glial cell) toxin alpha-aminoadipic acid. Changes in the electroretinogram and the response of Müller cells to a potassium stimulus are also similarly eliminated in methanol-treated FR rats and alpha-aminoadipic acid-treated FR and FS rats. These results suggest that the Müller cell may be the initial target in methanol-induced visual system toxicity.
Garner
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Department of Automotive Safety and Health Research, General Motors Corporation, Warren, Michigan 48090-9055.
Lee
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Louis-Ferdinand
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D015074:2-Aminoadipic Acid / Q000008:administration & dosage / Q000633:toxicity; D000255:Adenosine Triphosphate / Q000378:metabolism*; D000284:Administration, Oral; D000613:Aminobutyrates / Q000008:administration & dosage / Q000633:toxicity; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004596:Electroretinography; D005492:Folic Acid / Q000378:metabolism; D005494:Folic Acid Deficiency; D007452:Iodates / Q000378:metabolism / Q000633:toxicity; D008297:Male; D000432:Methanol / Q000008:administration & dosage / Q000633:toxicity*; D009457:Neuroglia / Q000166:cytology* / Q000378:metabolism; D026902:Potassium Channel Blockers; D011190:Potassium Cyanide / Q000633:toxicity; D051381:Rats; D012160:Retina / Q000166:cytology / Q000187:drug effects*
D000613:Aminobutyrates; D007452:Iodates; D026902:Potassium Channel Blockers; D015074:2-Aminoadipic Acid; D000255:Adenosine Triphosphate; D005492:Folic Acid; C012729:2-amino-4-phosphonobutyric acid; D011190:Potassium Cyanide; C032285:sodium iodate; D000432:Methanol