Identification of Estrogen Signaling in a Prioritization Study of Intraocular Pressure-Associated Genes.

Journal Article (Journal Article)

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 ESR1 mediating 25 interactions. Several genes (i.e., EFEMP1, FOXC1, and SPTBN1) regulated by β-estradiol/ESR1 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 ESR1 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.

Full Text

Duke Authors

Cited Authors

  • 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, Y

Published Date

  • September 24, 2021

Published In

Volume / Issue

  • 22 / 19

PubMed ID

  • 34638643

Pubmed Central ID

  • PMC8508848

Electronic International Standard Serial Number (EISSN)

  • 1422-0067

Digital Object Identifier (DOI)

  • 10.3390/ijms221910288


  • eng

Conference Location

  • Switzerland