Visual Performance Declines in 24 mo C57BL/6J Mice are Unrelated to Outer Retina Oxidative Stress in Vivo

Purpose : Age-related declines in visual performance increase the risk of morbidity and mortality from falls in humans and are so far untreatable; rats and mice also show reduced vision with age. The cause of age-related declines in visual performance is unclear but evidence ex vivo suggests a link to photoreceptor / retinal pigment epithelium oxidative stress. Methods : 2 and 24 mo male C57BL/6J mice were non-invasively evaluated for excessive production of paramagnetic free radicals based on whether R1 (= 1/T1) in retinal laminae are reduced after acute anti-oxidant (AO) administration [QUEnch-assiSTed (QUEST) magnetic resonance imaging (MRI)]. Superoxide production was measured in excised retina (lucigenin assay). Acute AO administration was also used to test for age-related oxidative stress-induced thinning of subretinal space (QUEST optical coherence tomography [OCT]) and cone-based visual performance declines (QUEST optokinetic tracking [OKT]). Results : At 2 mo, no evidence was found in vivo for oxidative stress in any retinal layer. At 24 mo, oxidative stress was localized only to superior outer retina. Yet, no age-related change in retinal superoxide production was noted suggesting that free radical species other than superoxide contributed to the positive QUEST MRI signal at 24 mo. Subretinal space did not show age-related thinning and was unresponsive to AO’s. Finally, visual performance declined with age and was not restored by AO’s that were effective in QUEST MRI. Conclusions : Outer retinal oxidative stress appears to be insufficient to explain the reduction in visual performance in 24 mo C57BL/6J mice