The contribution of AII amacrine cells to the ERG of the mouse

Abstract

Purpose : The transcription factor NFIA is selectively expressed in a few retinal cell types in maturity, including the AII amacrine cells. Ablation of Nfia from the embryonic mouse retina leads to a large (87%) reduction in AII amacrine cells in adulthood. This loss of AII amacrine cells is highly selective, as only one of twelve other cell types measured show a decrease in cell number (the Type 2 cone bipolar cell, by 34%); additionally, the thickness and architecture of the retinal layers appears unperturbed. The current study sought to determine the consequence of this selective loss of AII amacrine cells on the physiology of Nfia-deficient retinas using electroretinography (ERG).

Methods : Floxed Nfia mice were crossed with Rx-cre mice to create conditional knockout (CKO) mice in which Nfia is removed from the retina before birth. Control (CTRL) and CKO mice were dark adapted overnight, then anesthetized with ketamine and xylazine. Pupils were dilated with tropicamide and full field ERG recordings were performed using a Phoenix Ganzfeld system. Recordings were taken from dark adapted mice using 1 ms flashes, increasing in intensity from -1.7 to 2.2 log(cd●s/m²). Mice were then light adapted for 10 mins, then recordings were taken with the same intensity series as before, but with a constant background luminance of 1.3 log(cd/m²). Oscillatory potentials (OPs) were isolated from the ERG traces using a bandpass filter between 70 and 300Hz.

Results : Dark adapted mice (CTRL=14, CKO=11) showed no difference in the magnitude or implicit time in the a-wave of the ERG. The magnitude of the b-wave, however, was slightly reduced in CKO animals across all intensities measured. Additionally, the implicit time of the b-wave was delayed in CKO mice, but only at higher flash intensities. Most conspicuously, there was a decrease in the amplitude, but not the timing, of the OPs at all intensities in CKO mice. ERG recordings from light adapted mice (CTRL=10, CKO=7) showed similar results: no changes were observed in the a-wave, but CKO mice displayed a decrease in the amplitude, and an increase in the implicit time, of the b-wave. OPs were not identifiable in light adapted mice.

Conclusions : The present study suggests that AII amacrine cells play a critical role in generating the oscillatory potentials of the ERG, and exert a minor influence on the amplitude and timing of the b-wave.

This is a 2020 ARVO Annual Meeting abstract.