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Abstract #95752 Published in IGR 22-3
Identification of Estrogen Signaling in a Prioritization Study of Intraocular Pressure-Associated Genes
Youngblood HA; Parker E; Cai J; Perkumas K; Yu H; Sun J; Smith SB; Bollinger KE; Wiggs JL; Pasquale LR; Hauser MA; Stamer WD; Liu YInternational journal of molecular sciences 2021; 22:
Elevated intraocular pressure (IOP) is the only modifiable risk factor for primary open-angle glaucoma (POAG). Herein we sought to prioritize a set of previously identified IOP-associated genes using novel and previously published datasets. We identified several genes for future study, including several involved in cytoskeletal/extracellular matrix reorganization, cell adhesion, angiogenesis, and TGF-β signaling. Our differential correlation analysis of IOP-associated genes identified 295 pairs of 201 genes with differential correlation. Pathway analysis identified β-estradiol as the top upstream regulator of these genes with mediating 25 interactions. Several genes (i.e., , , and ) regulated by β-estradiol/ were highly expressed in non-glaucomatous human trabecular meshwork (TM) or Schlemm's canal (SC) cells and specifically expressed in TM/SC cell clusters defined by single-cell RNA-sequencing. We confirmed gene and protein expression in human TM cells and TM/SC tissue with quantitative real-time PCR and immunofluorescence, respectively. 17β-estradiol was identified in bovine, porcine, and human aqueous humor (AH) using ELISA. In conclusion, we have identified estrogen receptor signaling as a key modulator of several IOP-associated genes. The expression of ESR1 and these IOP-associated genes in TM/SC tissue and the presence of 17β-estradiol in AH supports a role for estrogen signaling in IOP regulation.
Department of Cellular Biology and Anatomy, Augusta University, Augusta, GA 30912, USA.
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