Formate-induced inhibition of photoreceptor function in methanol intoxication. J Pharmacol Exp Ther 1999 Apr;289(1):361-70
Date
03/23/1999Pubmed ID
10087025Scopus ID
2-s2.0-0032949572 (requires institutional sign-in at Scopus site) 54 CitationsAbstract
Formic acid is the toxic metabolite responsible for the retinal and optic nerve toxicity produced in methanol intoxication. Previous studies in our laboratory have documented formate-induced retinal dysfunction and histopathology in a rodent model of methanol intoxication. The present studies define the time and concentration dependence of formate-induced retinal toxicity in methanol-intoxicated rats. Retinal function was assessed 24, 48, and 72 h after the initial dose of methanol by flicker electroretinographic measurements. Retinal histopathology was assessed at the same time intervals. Rod- and cone-mediated electroretinogram (ERG) responses were attenuated in a formate concentration- and time-dependent manner, and both retinal sensitivity and maximal responsiveness to light were diminished. Attenuation of UV-cone-mediated responses was temporally delayed in comparison to the functional deficits observed in the 15 Hz/510 nm responses, which have a rod-mediated component and occurred at significantly higher formate concentrations. Both 15 Hz/510 nm and UV-cone-mediated ERG responses were undetectable by 72 h; however, if light intensity was increased, a retinal ERG response could be recorded, indicating that photoreceptor function was profoundly attenuated, but not abolished, under these intoxication conditions. Functional changes preceded structural alterations. Histopathological changes were most pronounced in the outer retina with evidence of inner segment swelling, photoreceptor mitochondrial disruption, and the appearance of fragmented photoreceptor nuclei in the outer nuclear layer. The nature of both the functional and structural alterations observed are consistent with formate-induced inhibition of mitochondrial energy production, resulting in photoreceptor dysfunction and pathology.
Author List
Seme MT, Summerfelt P, Henry MM, Neitz J, Eells JTAuthor
Janis Eells PhD Professor in the Biomedical Sciences department at University of Wisconsin - MilwaukeeMESH terms used to index this publication - Major topics in bold
AnimalsElectroretinography
Energy Metabolism
Formates
Light
Male
Methanol
Mitochondria
Photoreceptor Cells, Vertebrate
Rats
Rats, Long-Evans
Retina
Retinal Cone Photoreceptor Cells
Retinal Rod Photoreceptor Cells
Solvents
Ultraviolet Rays
