Age-Related Changes in the Pattern Electroretinogram of Normal and Glatiramer Acetate–Immunized Rats

Abstract

Age-related changes in retinal ganglion cell (RGC) activity may impact results of long-term functional studies of disease progression and drug efficacy in humans and animal models. Though these changes can be evaluated using the pattern electroretinogram (PERG), longitudinal studies suffer from failure of follow-up from birth to senescence. Our aim was to perform a long-term, longitudinal study evaluating age-related changes in the rat PERG, by conducting repeated, serial recordings in the same animals. Additionally, we tested the hypothesis that neuroprotective treatment using glatiramer acetate (COP-1) immunization may delay age-related decline in function. PERG was recorded from six untreated and seven Cop-1-immunized Lewis rats. Recordings were conducted at 2- to 4-week intervals from age 5 to 59 weeks. PERG amplitudes significantly increased between 5 to 7 weeks of age, and decreased from age 30 weeks onward (P = 0.016 and 0.0002, respectively). Amplitudes fluctuated insignificantly in weeks 7 to 30, with peak amplitudes reached at age 18 weeks in most spatial frequencies tested. N2 implicit times were shortened, mainly during weeks 5 to 18 and 40 to 59 (P < 0.001). PERG amplitudes of Cop-1-treated rats were similar to controls (P = 0.137) but peaked later (22-26 weeks). This 14-month-long study provided accurate measurement of developmental and aging changes of rat RGC function using repeated testing of individual animals. We found functional development to extend beyond the reported period of structural changes. Cop-1-immunized rats were not protected against age-related decline in inner retinal function, although their PERG maturation dynamics were altered.