Identification of estrogen signaling in a prioritization study of intraocular pressure-associated genes

Hannah A. Youngblood, Emily Parker, Jingwen Cai, Kristin Perkumas, Hongfang Yu, Jason Sun, Sylvia B. Smith, Kathryn E. Bollinger, Janey L. Wiggs, Louis R. Pasquale, Michael A. Hauser, W. Daniel Stamer, Yutao Liu

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Article number10288
JournalInternational journal of molecular sciences
Volume22
Issue number19
DOIs
StatePublished - Oct 1 2021
Externally publishedYes

Keywords

  • Aqueous humor outflow
  • Estrogen signaling
  • Intraocular pressure
  • Primary open-angle glaucoma

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

Fingerprint

Dive into the research topics of 'Identification of estrogen signaling in a prioritization study of intraocular pressure-associated genes'. Together they form a unique fingerprint.

Cite this