Conditional Deletion of AP-2α and AP-2β in the Developing Murine Retina Leads to Altered Amacrine Cell Mosaics and Disrupted Visual Function

Purpose: The combined action of the activating protein-2 (AP-2) transcription factors, AP-2α and AP-2β, is important in early retinal development, specifically in the formation of horizontal cells. However, in previous studies, it was not possible to analyze postnatal development and function of additional retinal subtypes. Methods: We used a double conditional deletion of AP-2α and AP-2β from the retina to further examine the combinatory role of these genes in retinal cell patterning and function in postnatal adult mice as measured by Voronoi domain area and nearest-neighbor distance spatial analyses and ERGs, respectively. Results: Conditional deletion of both AP-2α and AP-2β from the retina resulted in a variety of abnormalities, including the absence of horizontal cells, defects in the photoreceptor ribbons in which synapses failed to form, along with evidence of aberrant amacrine cell arrangement. Although no significant changes in amacrine cell population numbers were observed in the double mutants, significant irregularities in the mosaic patterning of amacrine cells was observed as demonstrated by both Voronoi domain areas and nearest-neighbor distances analyses. These changes were further accompanied by an alteration in the retinal response to light as recorded by ERGs. In particular, in the double-mutant mice lacking AP-2α and AP-2β, the b-wave amplitude, representative of interneuron signal processing, was significantly reduced compared with control littermates. Conclusions: Together these findings demonstrate the requirement for both AP-2α and AP-2β in proper amacrine mosaic patterning and a normal functional light response in the retina.