Abstract
Abstract: :
Purpose:We hypothesize that two important contributing factors to the Cuban Epidemic Optic Neuropathy (CEON) were folate-deficiency and chronic low-level methanol exposure leading to formic acidemia. Each of these factors has been related to the production of energy deficient states culminating in retinal and optic nerve dysfunction. To test this hypothesis, we have developed a folate-deficient rodent model chronically exposed to low doses of methanol. The purpose of this investigation was to assess retinal toxicity in this animal model. Methods: Rats were made folate deficient by maintenance on a folate-deficent diet for 8-10 weeks. Folate deficent (FD) and control diet (CD) rats were then treated with low doses of methanol (1g/kg every 72 hr) for 3 - 4 weeks and blood formate concentrations were monitored. At the end of the methanol treatment period, visual function was assessed by flicker electroretinography. Results: Serum folate concentrations were significantly reduced from control diet values of 176 8 ng/ml to 7 0.9 ng/ml in FD rats. Methanol treatment had no effect on folate concentrations in CD rats (197 8 ng/ml), but further attenuated folate concentrations in FD rats (1 0.4 ng/ml). Blood formate concentrations were significantly elevated in FD rats treated with methanol (2.01 0.30 mM) compared to FD rats (0.23 0.08 mM), CD rats (0.11 0.03 mM) or CD rats treated with methanol (0.31 0.03 mM). ERG measurements in FD rats treated with methanol revealed profound attenuation (23% of CD response) of both rod/M-cone mediated (510 nm/15 hz) and UV-cone mediated (380 nm/25 hz) responses compared to each of the other treatment groups. CD rats treated with methanol also demonstrated a significant attenuation (46% of CD response) in both rod/M-cone mediated and UV-cone mediated ERG responses. Conclusion: These findings support our hypothesis that folate-deficiency coupled with chronic exposure to low concentrations of methanol can profoundly disrupt retinal function. They further indicate that chronic exposure to low concentrations of methanol can disrupt retinal function in folate-sufficient animals. [Support: NIH: 1RO1-ES06648(JTE), P30-EY01193 (MCW) and 1RO1-EY11396(AS)].
Keywords: 554 retina • 506 pathology: experimental • 396 electroretinography: non-clinical