Conditional Deletion of AP-2a and AP-2b in the DevelopingMurine Retina Leads to Altered Amacrine Cell Mosaics andDisrupted Visual Function

Investigative Ophthalmology & Visual Science

article

Emily Anne Hicks¹  Mizna Zaveri²  Paula A. Deschamps²  Michael D. Noseworthy¹  Alexander Ball²  Trevor Williams⁵  Judith A. West-Mays¹ 

[1] McMaster School of Biomedical Engineering, McMaster University;Department of Pathology and Molecular Medicine, McMaster University;Department of Electrical and Computer Engineering, McMaster University;Department of Radiology, McMaster University;Department of Craniofacial Biology and Department of Cell and Developmental Biology, University of Colorado Denver, Anschutz Medical Campus

关键词: retina development;    amacrine cells;    horizontal cells;    mosaic patterningelectroretinograms;   

DOI  :  10.1167/iovs.17-23283

学科分类：社会科学、人文和艺术（综合）

来源: Association for Research in Vision and Ophthalmology

【 摘 要 】

PURPOSE. The combined action of the activating protein-2 (AP-2) transcription factors, AP-2aand AP-2b, is important in early retinal development, specifically in the formation ofhorizontal cells. However, in previous studies, it was not possible to analyze postnataldevelopment and function of additional retinal subtypes.METHODS. We used a double conditional deletion of AP-2a and AP-2b from the retina to furtherexamine the combinatory role of these genes in retinal cell patterning and function inpostnatal adult mice as measured by Voronoi domain area and nearest-neighbor distancespatial analyses and ERGs, respectively.RESULTS. Conditional deletion of both AP-2a and AP-2b from the retina resulted in a variety ofabnormalities, including the absence of horizontal cells, defects in the photoreceptor ribbonsin 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 thedouble mutants, significant irregularities in the mosaic patterning of amacrine cells wasobserved as demonstrated by both Voronoi domain areas and nearest-neighbor distancesanalyses. These changes were further accompanied by an alteration in the retinal response tolight as recorded by ERGs. In particular, in the double-mutant mice lacking AP-2a and AP-2b,the b-wave amplitude, representative of interneuron signal processing, was significantlyreduced compared with control littermates.CONCLUSIONS. Together these findings demonstrate the requirement for both AP-2a and AP-2bin proper amacrine mosaic patterning and a normal functional light response in the retina.

【 授权许可】

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