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

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

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 sev...

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Bibliographic Details
Main Authors: 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
Format: Article
Language:English
Published: MDPI AG 2021-09-01
Series:International Journal of Molecular Sciences
Subjects:
primary open-angle glaucoma
intraocular pressure
aqueous humor outflow
estrogen signaling
Online Access:https://www.mdpi.com/1422-0067/22/19/10288
Description
Summary: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 <i>ESR1</i> mediating 25 interactions. Several genes (i.e., <i>EFEMP1</i>, <i>FOXC1</i>, and <i>SPTBN1</i>) regulated by β-estradiol/<i>ESR1</i> 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 <i>ESR1</i> 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.
ISSN:1661-6596
1422-0067

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