Long–term n–3 fatty acid deficiency alters rod phototransduction sensitivity in the rhesus monkey

Abstract

Abstract: : Purpose: To investigate the effect of long–term n–3 fatty acid deficiency on phototransduction mechanisms in rhesus monkeys. Methods: From birth through 8–11 years of age, monkeys were fed 1 of 3 semipurified diets containing 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 diet was shown previously to reduce retinal DHA by 80%. Full field rod ERG a–waves were recorded to saturating flashes over a 4.3 log intensity range (max 5.8 log sc Td–s). Maximum rod ERG amplitude (R_mP3) and phototransduction sensitivity (S) were derived from the ensemble fit of a P3 model to the leading edges of ERG a–waves (intensities <3.6 log sc Td–s). The maximum rate or rise of each ERG a–wave was calculated from the peak of the differential of the a–wave leading edge. A saturating function was fitted to the plot of maximum rate of rise against flash intensity. The 2 parameters derived were 1) the saturating value for the maximum rate of rise (dR/dt_SAT), a measure of max PDE activity, and 2) the intensity (I_0.7) at 70% of dR/dt_SAT. The time constant of rod recovery and duration of rod saturation were measured with a paired flash protocol using identical 2.8 log sc Td–s flashes. Results: The high ALA and DHA groups had equivalent results and were combined for analysis. In low ALA monkeys, both S and I_0.7 were reduced by 30% (P<0.03) compared with the high ALA/DHA monkeys, indicating a reduction in phototransduction sensitivity. There were no significant differences in R_mP3, dR/dt_SAT or the rod recovery parameters. There were no significant correlations between S and the rod recovery parameters. Conclusions: The maximum rate of PDE activity, as determined from dR/dt_SAT, was not altered by n–3 deficiency. This result suggests that the reduction in phototransduction sensitivity occurs either due to a reduction in effective rhodopsin density or activation efficiency, or downstream of PDE hydrolysis (e.g. via altered cGMP gated ion channel closure). Reduction in phototransduction sensitivity was not present in an earlier study of the same animals at 3–5 years of age¹, suggesting an age–related susceptibility to n–3 deficiency. At the earlier age we also reported delayed rod recovery to high intensity flashes ranging from 4.4 to 5.6 log sc Td–s (1.6–3.8 log units higher than used here)¹. Substrate saturation for rhodopsin kinase starts between 0.5–2.0% bleach (ca. 4.6–5.2 log sc Td–s). Combined rod recovery results from the two studies suggest that delay in rod recovery in n–3 deficient monkeys may only be detectable once substrate saturation occurs in the deactivation pathway. ¹Jeffrey BG et al. IOVS 2002:43:2806

Keywords: photoreceptors • lipids • electroretinography: non–clinical