Development of electroretinogram and rod phototransduction response in human infants

Abstract

Purpose: To describe and analyze developmental change from birth through maturity of human electroretinogram (ERG) response, especially in terms of rod phototransduction as represented in the ERG a-wave.

Methods: Electroretinograms were recorded from 16 human infants from 5 to 270 days of age, two children 1.9 and 3.4 years of age, and 13 older subjects between 10 and 43 years of age. A range of full-field, white-light flashes up to intensities sufficient to saturate a-wave and b-wave amplitudes and a-wave rate-of-rise was used. The a-wave leading edge, the a-wave and b-wave amplitudes, and the b/a-wave ratio at maximum intensity were analyzed using a model of the activation steps of the G-protein phototransduction cascade. This model, applied to a-waves, provides three parameters interpretable in terms of rod phototransduction: amax (a-wave maximum amplitude, proportional to circulating dark current), A' (estimated constant of transduction amplification), and t'eff (sum of brief delays associated with the cascade steps).

Results: Both amax and bmax (maximum b-wave amplitude) increased rapidly from birth. bmax reached apparently mature values by approximately 6 months, but amax, and thus (b/a)max (b/a ratio at maximum intensity), did not reach mature values until sometime after the third or fourth year. Similarly, A' was immature at birth at approximately 25% to 50% of adult levels at intensities below rate-of-rise saturation. For the youngest infants, rate-of-rise saturation appeared to occur at lower effective isomerizations per rod compared to that of the adult. Following a time course similar to that of amax, full maturity for A' probably was not reached before 5 years of age.

Conclusions: Results from the a-wave analysis are consistent with immaturities in the rod photoreceptors early in life. The difference from those of the adult may be explained by lower neonatal concentrations in one or more of the transduction substrates, decreased outer segment length, and, possibly, decreased density of some membrane proteins mediating the cationic dark current. Early adultlike b-wave amplitudes suggest early maturity for the inner retinal elements (rod bipolar and Müller cells) underlying b-wave response, compared to the photoreceptors.