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 Nati onal Center for Toxicological Research (NCTR). Age-dependent declines in ou ter nuclear layer (ONL = photoreceptor) cell densities, ONL height, inner n uclear layer (INL) cell densities, and thicknesses of the inner retina and whole retina were quantified in thick sections at six loci across the circu mference of the sensory retina (four peripheral. two central). Data were an alyzed by repeated measures, general linear models. Aging in both diet grou ps was associated with declines in ONL cell density, ONL height, peripheral INL cell density and total retinal thickness (P less than or equal to 0.05 ). However, ONL cell densities, ONL height and retinal thickness were signi ficantly greater in the CR versus AL diet group at all three ages (P less t han or equal to 0.005). CR was also associated with a trend for greater per ipheral INL cell density (P = 0.06) and with greater INL thickness at 30 mo nths (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 differe nces in retinal length, i.e. delayed retinal growth in response to CR. Enha nced ONL cell density, ONL height, INL cell density, INL thickness and tota l retinal thickness in the CR-30 cohort appear to be as a result of reduced rates of retinal cell loss bi tween 24 and 30 months. However, the protect ive effect of CR in retinas of older animals may also reflect the initial g rowth-associated enhancements which were observed in 12 month-old animals. The rat retina may provide a useful model for elucidating the neuroprotecti ve mechanism(s) of CR. (C) 2000 Elsevier Science Ireland Ltd. All rights re served.