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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-\u03b2 signaling. Our differential correlation analysis of IOP-associated genes identified 295 pairs of 201 genes with differential correlation. Pathway analysis identified \u03b2-estradiol as the top upstream regulator of these genes with ESR1 mediating 25 interactions. Several genes (i.e., EFEMP1, FOXC1, and SPTBN1) regulated by \u03b2-estradiol\/ESR1 were highly expressed in non-glaucomatous human trabecular meshwork (TM) or Schlemm\u2019s 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. 17\u03b2-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 17\u03b2-estradiol in AH supports a role for estrogen signaling in IOP regulation.<\/jats:p>","DOI":"10.3390\/ijms221910288","type":"journal-article","created":{"date-parts":[[2021,9,27]],"date-time":"2021-09-27T04:55:33Z","timestamp":1632718533000},"page":"10288","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Identification of Estrogen Signaling in a Prioritization Study of Intraocular Pressure-Associated Genes"],"prefix":"10.3390","volume":"22","author":[{"given":"Hannah A.","family":"Youngblood","sequence":"first","affiliation":[{"name":"Department of Cellular Biology and Anatomy, Augusta University, Augusta, GA 30912, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily","family":"Parker","sequence":"additional","affiliation":[{"name":"Department of Cellular Biology and Anatomy, Augusta University, Augusta, GA 30912, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingwen","family":"Cai","sequence":"additional","affiliation":[{"name":"Department of Cellular Biology and Anatomy, Augusta University, Augusta, GA 30912, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristin","family":"Perkumas","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Duke University Medical Center, Durham, NC 27710, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongfang","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Cellular Biology and Anatomy, Augusta University, Augusta, GA 30912, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Cellular Biology and Anatomy, Augusta University, Augusta, GA 30912, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylvia B.","family":"Smith","sequence":"additional","affiliation":[{"name":"Department of Cellular Biology and Anatomy, Augusta University, Augusta, GA 30912, USA"},{"name":"Department of Ophthalmology, Augusta University, Augusta, GA 30912, USA"},{"name":"James & Jean Culver Vision Discovery Institute, Augusta University, Augusta, GA 30912, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathryn E.","family":"Bollinger","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Augusta University, Augusta, GA 30912, USA"},{"name":"James & Jean Culver Vision Discovery Institute, Augusta University, Augusta, GA 30912, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janey L.","family":"Wiggs","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Boston, MA 02114, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louis R.","family":"Pasquale","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael A.","family":"Hauser","sequence":"additional","affiliation":[{"name":"Department of Medicine, Duke University, Durham, NC 27710, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W. Daniel","family":"Stamer","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Biomedical Engineering, Duke University, Durham, NC 22710, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2870-4504","authenticated-orcid":false,"given":"Yutao","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Cellular Biology and Anatomy, Augusta University, Augusta, GA 30912, USA"},{"name":"James & Jean Culver Vision Discovery Institute, Augusta University, Augusta, GA 30912, USA"},{"name":"Center for Biotechnology and Genomic Medicine, Augusta University, Augusta, GA 30912, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,9,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1136\/bjo.2005.081224","article-title":"The number of people with glaucoma worldwide in 2010 and 2020","volume":"90","author":"Quigley","year":"2006","journal-title":"Br. 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