Atonal homolog 7 (ATOH7) confers neuroprotection for photoreceptor cells in glaucoma via inhibition of the notch pathway

Abstract

AbstractSingle‐cell RNA sequencing (scRNA‐seq) technologies enable the profiling and analysis of the transcriptomes of single cells and hold promise for clarifying gene mechanisms at single‐cell resolution. We based this study on scRNA‐seq data to reveal glaucoma‐related genes and downstream pathways with neuroprotection effects. The scRNA‐seq datasets related to glaucoma of retinal tissue samples of human beings and Atonal Homolog 7 (ATOH7)‐null mice were obtained from the GEO database. The 74 top marker genes and 20 cell clusters were obtained in human retinal tissue samples. The key gene ATOH7 was found after the intersection with genes from GeneCards data. In the ATOH7‐null mouse retinal tissue samples, pseudotime inference demonstrated significant changes in cell differentiation. Moreover, mouse retinal photoreceptor cells (PRCs) were cultured and treated with lentivirus carrying oe‐ATOH7 alone or in combination with Notch signaling pathway activator Jagged‐1/FC, after which cell biological functions were determined. The involvement of ATOH7 in glaucoma was identified through regulating PRCs. Furthermore, ATOH7 conferred neuroprotection in PRCs in glaucoma by mediating the Notch signaling pathway. In vitro data confirmed that ATOH7 overexpression promoted the differentiation of PRCs and inhibited their apoptosis by suppressing the Notch signaling pathway. The evidence provided by our study highlighted the involvement of ATOH7 in the blockade of the Notch signaling pathway, resulting in the neuroprotection for PRCs in glaucoma.image