Nfia is Critical for AII Amacrine Cell Production: Selective Bipolar Cell Dependencies and Diminished ERG

Abstract

The NFI transcripton (actor genes Nfia: Nfib and NHx are all enriched in late- stage retinal progenitor cells, and their toss has been shewn to retain these progenitors at the expense of later-generated retinal cell types. Whether they play any role in the specification of those later generated fates is unknown, but the expression of one of these. Nfia. in a specific amacrine cell type may intimate such a role. Here. Nfia-CKO mice (both sexes) were assessed, finding a massive and largely selective absence of An amacrine cells. There was. however, a partial reduction in Type 2 cone bipolar cells (CBCs). being richly interconnected to AIT cells. Counts of dying cells shewed a significant increase in Nfia-CKO retinas at P7, after AH cell numbers were already reduced but in advance of the loss o( Type 2 CBCs detected by P10. Those results suggest a role for Nfia in the specification o(the All amacrine cell fate, and a dependency d the Type 2 CBCs upon them. Delaying the conditional toss of Nfia to the first postnatal week did not alter AH cell number nor differentiation, further suggesting that its role in AH cells is solely associated with their production. The physiological consequences d their loss were assessed using the ERG, finding the oscillatory potentials to be profoundly diminished. A slight reduction in the b-wave was also detected, attributed to an altered distribution of the terminate of rod bipolar celte, implicating a role d the All amacrine cells in constraining their stratification.