Abstract
Abstract: :
Purpose: This study investigated age- and strain-related differences in retinal second messenger function and electrophysiology in the rat, as a prelude to studies of the influence of age on the effects of organophosphorous pesticides (OPs) on retinal function. We hypothesize that in aged rats OP exposure may result in retinal degeneration, possibly related to dysfunction in inositolphosphate (IP) signaling pathways. Strain comparisons were necessary because of limited availability of aged rats and included pigmented and non-pigmented strains. Methods: Strains tested were Fisher-344 (F-344; albino; 70-day, 1- and 2-year old), Brown Norway (BN; pigmented; 70-day and 2-year old), and Long-Evans (LE; pigmented; 70-day old; IP assay only). Carbachol-stimulated IP release was measured in dark-adapted whole retina and is reported as percent released of total 3H-myo-inositol incorporated (n=6–8/age/strain). Flash ERGs were obtained under dark- and light-adapted conditions using flashes of increasing intensity. (n=4–6/age/strain). Results: Basal IP release was similar across strains and ages. Carbachol-stimulated IP release was 36.9% higher in F-344 compared to BN; stimulated release in young LE was similar to that of young F-344. No age-dependent differences in stimulated release were noted in F-344 and BN. In dark-adapted ERGs, B-wave amplitudes were 20.5% higher in F-344 compared to BN; A-wave amplitudes were similar across strains. Strain differences in A- and B-wave latencies varied depending on flash intensity, with BN having greater latencies than F-344 at higher flash intensities. Within strains, aged rats had lower A-wave amplitudes (F-344: 45.2%; BN: 45.6%) as well as lower B-wave amplitudes (F-344: 20.1%; BN: 33.5%) compared to young rats. A- and B-wave latencies were similar across ages in F-344 but depended on flash intensity in BN. Oscillatory potentials were strongly diminished in aged BN compared to all other groups. In light-adapted ERGs, F-344 had higher amplitudes than BN across peaks. Within strains, aged rats had lower amplitudes across peaks compared to young rats. Conclusions: In summary, F-344 and LE had higher IP release than BN. A- and B-wave amplitudes were also higher in F-344 compared to BN. Within strains, aged rats had lower ERG responses, but similar levels of IP release compared to young rats. These results suggest that IP release in the retina depends on strain but not on age or pigmentation, and that electrophysiologic function depends on both strain and age. This is an abstract for a proposed presentation and does not necessarily reflect EPA policy.
Keywords: aging • electroretinography: non-clinical • second messengers: pharmacology/physiology