Dynamic and Steady State Light Adaptation in N–3 Fatty Acid Deficient Monkeys

Abstract

Abstract: : Purpose: N–3 fatty acid deficiency leads to abnormalities in retinal function, including phototransduction and rod recovery. This study investigated effects of long–term n–3 fatty acid deficiency on dynamic and steady–state light adaptation of the ERG rod photoresponse in rhesus monkeys. Methods: From birth through 9–12 years of age, monkeys were fed diets with 0.3% ALA (n=9), 8% ALA (n=7) or 0.6% DHA (n=5) as the principal n–3 fatty acid. The low ALA (n–3 deficient) diet previously was shown to reduce retinal DHA by 80%. Dynamic light–adapted rod photoresponses were measured to a 1 sec step ("white" LED, 0.1 cd/m²). Steady–state light–adapted rod photoresponses to brief flashes (11 scot Td–s) and rod recovery to bright flashes (4.4 log scot Td–sec) were measured against a constant background (0.1 cd/m²). Both step and flash photoresponses and rod recovery were measured with the paired–flash ERG method. For photoresponses, a probe flash (3.9 log sc Td–s) followed at intervals ranging from 40–900 msec for the step and 20–400 msec for the test flash. Photoresponse amplitudes were normalized with respect to maximal probe flash amplitude. Derived parameters included peak relative amplitude and time to peak. The time constant of rod recovery and duration of rod saturation were measured with identical 4.4 log sc Td–s flashes at intervals from 1.5 to 90 sec. Results: The high ALA and DHA groups had equivalent results and were combined for analysis. The high ALA/DHA and low ALA groups did not differ in sensitivity or time to peak of the step onset or flash photoresponses. For all groups combined, the test flash photoresponse peaked at 75 msec with relative amplitude 0.57, a 60% reduction in sensitivity compared to dark–adapted sensitivity. The step response rose to a peak relative amplitude of 0.38 at 325 msec before declining to a plateau level of 0.31 by 900 msec. The time constant of light–adapted rod recovery was 44% longer (p<0.001) in the low ALA monkeys (6.50±0.49 sec) than in the high ALA/DHA monkeys (4.52±0.37 sec), a difference larger than the 21% delay in dark–adapted rod recovery to the same flash intensity previously found in the low ALA group (Jeffrey et al., ARVO 2004). Conclusions: N–3 deficient monkeys show a consistent delay in rod recovery to bright saturating flashes in both light– and dark–adapted conditions, but no differential effect of light adaptation on sensitivity or response kinetics to subsaturating flashes. This result adds to evidence for a specific effect of n–3 deficiency on deactivation under conditions of substrate saturation, perhaps due to alterations in ROS membrane biophysical properties.

Keywords: electroretinography: non-clinical • lipids • photoreceptors