{"doi":"10.3390/ijms221910288","title":"Identification of Estrogen Signaling in a Prioritization Study of Intraocular Pressure-Associated Genes","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.","journal":"International Journal of Molecular Sciences","year":2021,"id":177796,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":20,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9518,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":464230,"name":"Emily Parker","orcid":"0000-0002-0707-4876","position":1,"is_corresponding":false},{"id":397912,"name":"Jingwen Cai","orcid":"0009-0004-0580-6270","position":2,"is_corresponding":false},{"id":468363,"name":"Kristin Perkumas","orcid":null,"position":3,"is_corresponding":false},{"id":722770,"name":"Hongfang Yu","orcid":null,"position":4,"is_corresponding":false},{"id":722771,"name":"Jason Sun","orcid":null,"position":5,"is_corresponding":false},{"id":380043,"name":"Sylvia B. Smith","orcid":null,"position":6,"is_corresponding":false},{"id":376784,"name":"Kathryn Bollinger","orcid":"0000-0002-2289-4899","position":7,"is_corresponding":false},{"id":6851,"name":"Janey L. Wiggs","orcid":"0000-0003-1890-3278","position":8,"is_corresponding":false},{"id":6895,"name":"Louis R. Pasquale","orcid":"0000-0002-5835-3496","position":9,"is_corresponding":false},{"id":6853,"name":"Michael A. Hauser","orcid":"0000-0003-2667-5420","position":10,"is_corresponding":false},{"id":292183,"name":"W. Daniel Stamer","orcid":"0000-0002-2504-8997","position":11,"is_corresponding":false},{"id":6873,"name":"Yutao Liu","orcid":"0000-0003-2870-4504","position":12,"is_corresponding":false},{"id":262150,"name":"Hannah Youngblood","orcid":"0000-0002-8326-7282","position":0,"is_corresponding":true}],"reference_count":186,"raw_metadata":null,"created_at":"2026-07-18T23:47:32.096934Z","pmid":"34638643","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}