Correcting quest magnetic resonance imaging-sensitive free radical production in the outer retina in vivo does not correct reduced visual performance in 24-month-old c57bl/6j mice

Abstract

PURPOSE. To test the hypothesis that acutely correcting a sustained presence of outer retina free radicals measured in vivo in 24-month-old mice corrects their reduced visual performance. METHODS. Male C57BL/6J mice two and 24 months old were noninvasively evaluated for unremitted production of paramagnetic free radicals based on whether 1/T1 in retinal laminae are reduced after acute antioxidant administration (QUEnch-assiSTed [QUEST] magnetic resonance imaging [MRI]). Superoxide production was measured in freshly excised retina (lucigenin assay). Combining acute antioxidant administration with optical coherence tomography (i.e., QUEST OCT) tested for excessive free radical-induced shrinkage of the subretinal space volume. Combining antioxidant administration with optokinetic tracking tested for a contribution of uncontrolled free radical production to cone-based visual performance declines. RESULTS. At two months, antioxidants had no effect on 1/T1 in vivo in any retinal layer. At 24 months, antioxidants reduced 1/T1 only in superior outer retina. No age-related change in retinal superoxide production was measured ex vivo, suggesting that free radical species other than superoxide contributed to the positive QUEST MRI signal at 24 months. Also, subretinal space volume did not show evidence for age-related shrinkage and was unresponsive to antioxidants. Finally, visual performance declined with age and was not restored by antioxidants that were effective per QUEST MRI. CONCLUSIONS. An ongoing uncontrolled production of outer retina free radicals as measured in vivo in 24 mo C57BL/6J mice appears to be insufficient to explain reductions in visual performance.