The Role of AP-2⍺ and AP-2β in Amacrine Cell Development and Patterning

Abstract

Previous studies from our lab have shown that Activating protein-2 (AP-2) transcription factors, AP-2α and AP-2β are important in retinal development, specifically in the developing horizontal and post-mitotic amacrine cells. Conditional deletion of AP-2α and AP-2β from the retina of mice resulted in a variety of abnormalities including loss of horizontal cells, defects in the photoreceptor ribbons in which synapses failed to form, along with evidence that amacrine cell mosaic patterning may be disrupted. The current thesis examined the neural retina of these AP-2α and AP-2β conditional mice in greater detail using immunofluorescence of histological sections and whole retinas, and electroretinograms to measure retinal function in post-natal adult mice. Examining regularity of the amacrine cell mosaics of these double mutants showed the loss of AP-2α and AP-2β led to significant irregularities in the mosaic patterning of these cells as determined by Voronoi domain areas (P<0.01) and nearest-neighbour distances (P<0.03). No significant changes in amacrine population numbers were observed. Observed cellular changes in the double conditional knock out mice were reflected as a change in the retinal response to light as recorded by electroretinograms. For example, the b-wave amplitude, representative of the interneuron signal processing, was significantly affected in those mice lacking AP-2⍺ and AP-2β (P<0.0001). Taken together, the work presented in this thesis implicates the requirement of AP-2⍺ and AP-2β for the correct amacrine mosaic patterning and for the proper functional light response in the retina.