Calorie restriction modulates age-dependent changes in the retinas of Brown Norway rats

The present study examined the effect of a 40% reduction in caloric intake (CR) versus ad libitum (AL) feeding on retinal aging. CR- and AL-fed Brown Norway (BN) rats were obtained at 12, 24 and 30 months of age from the National Center for Toxicological Research (NCTR). Age-dependent declines in outer nuclear layer (ONL=photoreceptor) cell densities, ONL height, inner nuclear layer (INL) cell densities, and thicknesses of the inner retina and whole retina were quantified in thick sections at six loci across the circumference of the sensory retina (four peripheral, two central). Data were analyzed by repeated measures, general linear models. Aging in both diet groups was associated with declines in ONL cell density, ONL height, peripheral INL cell density and total retinal thickness (P< or =0.05). However, ONL cell densities, ONL height and retinal thickness were significantly greater in the CR versus AL diet group at all three ages (P< or =0.005). CR was also associated with a trend for greater peripheral INL cell density (P=0.06) and with greater INL thickness at 30 months (Bonferroni P=0.03). Elevated ONL cell densities in the CR-12 cohort relative to the AL-12 cohort could be explained by diet-associated differences in retinal length, i.e. delayed retinal growth in response to CR. Enhanced ONL cell density, ONL height, INL cell density, INL thickness and total retinal thickness in the CR-30 cohort appear to be as a result of reduced rates of retinal cell loss between 24 and 30 months. However, the protective effect of CR in retinas of older animals may also reflect the initial growth-associated enhancements which were observed in 12 month-old animals. The rat retina may provide a useful model for elucidating the neuroprotective mechanism(s) of CR.