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A. Rodriguez, J.T. Eells, D.K. Vaughan; Methanol Retinotoxicity in the Cone–Dominant Ground Squirrel Retina . Invest. Ophthalmol. Vis. Sci. 2005;46(13):2986.
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Purpose: A growing body of evidence supports a central role for mitochondrial dysfunction in retinal aging and in the pathogenesis of numerous retinal and optic nerve diseases. Formic acidemia resulting from methanol intoxication provides a reproducible and dose–dependent model of exogenously induced photoreceptor mitochondrial dysfunction. Formic acidemia is also the cause of blindness in human methanol intoxication. We have previously described a rat model of mitochondrial dysfunction in (rod) photoreceptors. The present studies were undertaken to investigate mitochondrial dysfunction in cones, and to better approximate methanol retinotoxicity of cone–dominant central human vision. To accomplish this objective we have evaluated cone mitochondrial dysfunction in response to methanol intoxication using the ground squirrel retina as a model. Methods: Adult thirteen–lined ground squirrels (ca. 200g, N = 4) were injected i.p., daily, with methanol and maintained in a N2O/O2 atmosphere. After 48 or 72 hours of treatment, animals were sacrificed. Blood was collected for measurements of formic acid. Retinas were collected for histological detection of photoreceptor disruption and degeneration. Results: All animals developed outward signs of intoxication, mitigated by the mild sedation of N2O, as well as the expected serum accumulation of formic acid. Consistent with data from the rods of rat retina, intoxicated ground squirrel retina exhibited cone outer segment disruption, edematous cone ellipsoid mitochondria and pedicles, inner nuclear layer edema, and evidence of early–stage pycnosis in the inner nuclear layer. Conclusions: Methanol intoxication of the cone–dominant ground squirrel produces the expected accumulation of formic acid in the blood, with concomitant cone and RPE abnormalities consistent with those previously observed in the rod–dominant rat model. The next step in our investigations will be to test the efficacy of near–infrared light treatment as a non–invasive, drug–free therapy for retinal cone injury.
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