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Prolonged IOP elevation results in optic nerve head damage and vision loss. Uniquely, PEXG is a form of open angle glaucoma that has variable penetrance, is difficult to treat and does not respond well to common IOP-lowering pharmaceuticals. Therefore, understanding modulators of disease severity will aid in targeted therapies for PEXG. Genome-wide association studies have identified polymorphisms in the long non-coding RNA lysyl oxidase-like 1-antisense 1 (LOXL1-AS1) as a risk factor for PEXG. Risk alleles, oxidative stress and mechanical stretch all alter LOXL1-AS1 expression. As a long non-coding RNA, LOXL1-AS1 binds hnRNPL and regulates global gene expression. In this study, we focus on the role of LOXL1-AS1 in the ocular cells (trabecular meshwork and Schlemm\u2019s canal) that regulate IOP. We show that selective knockdown of LOXL1-AS1 leads to cell-type-specific changes in gene expression, ECM homeostasis, signaling and morphology. These results implicate LOXL1-AS1 as a modulator of cellular homeostasis, altering cell contractility and ECM turnover, both of which are well-known contributors to PEXG. These findings support LOXL1-AS1 as a key target for modifying the disease.<\/jats:p>","DOI":"10.1093\/hmg\/ddad128","type":"journal-article","created":{"date-parts":[[2023,8,2]],"date-time":"2023-08-02T12:11:08Z","timestamp":1690978268000},"page":"3053-3062","source":"Crossref","is-referenced-by-count":8,"title":["<i>Lysyl oxidase-like 1-antisense 1<\/i> (<i>LOXL1-AS1<\/i>) lncRNA differentially regulates gene and protein expression, signaling and morphology of human ocular cells"],"prefix":"10.1093","volume":"32","author":[{"given":"Heather M","family":"Schmitt","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, Duke University , Durham, NC 27710 , USA"},{"name":"Department of Medicine, Duke University , Durham, NC 27710 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kristyn M","family":"Hake","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Duke University , Durham, NC 27710 , USA"},{"name":"Department of Medicine, Duke University , Durham, NC 27710 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kristin M","family":"Perkumas","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Duke University , Durham, NC 27710 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brandon M","family":"L\u00ea","sequence":"additional","affiliation":[{"name":"Department of Medicine, Duke University , Durham, NC 27710 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria F","family":"Suarez","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Duke University , Durham, NC 27710 , USA"},{"name":"Department of Medicine, Duke University , Durham, NC 27710 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael L","family":"De Ieso","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Duke University , Durham, NC 27710 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rashad S","family":"Rahman","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Duke University , Durham, NC 27710 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William M","family":"Johnson","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Duke University , Durham, NC 27710 , USA"},{"name":"Department of Medicine, Duke University , Durham, NC 27710 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mar\u00eda","family":"Gomez-Caraballo","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Duke University , Durham, NC 27710 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Allison E","family":"Ashley-Koch","sequence":"additional","affiliation":[{"name":"Department of Medicine, Duke University , Durham, NC 27710 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael A","family":"Hauser","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Duke University , Durham, NC 27710 , USA"},{"name":"Department of Medicine, Duke University , Durham, NC 27710 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2504-8997","authenticated-orcid":false,"given":"W Daniel","family":"Stamer","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Duke University , Durham, NC 27710 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2023,8,4]]},"reference":[{"key":"2023101912575981500_ref1","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1016\/j.exer.2016.11.011","article-title":"Major review, exfoliation syndrome, advances in disease genetics, molecular biology, and epidemiology","volume":"154","author":"Aboobakar","year":"2017","journal-title":"Exp. Eye Res."},{"key":"2023101912575981500_ref2","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1097\/IJG.0000000000000711","article-title":"lncRNAs, DNA methylation, and the pathobiology of exfoliation glaucoma","volume":"27","author":"Johnson","year":"2018","journal-title":"J. Glaucoma"},{"key":"2023101912575981500_ref3","doi-asserted-by":"crossref","first-page":"776","DOI":"10.1016\/j.exer.2008.08.012","article-title":"Molecular pathology of pseudoexfoliation syndrome\/glaucoma \u2013 new insights from LOXL1 gene associations","volume":"88","author":"Schlotzer-Schrehardt","year":"2009","journal-title":"Exp. Eye Res."},{"key":"2023101912575981500_ref4","article-title":"Pseudoexfoliation (PEX) syndrome and Pseudoexfoliation glaucoma","author":"Ou","year":"2021","journal-title":"BrightFocus Foundation"},{"key":"2023101912575981500_ref5","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1093\/ajhp\/62.7.691","article-title":"Glaucoma and its treatment: a review","volume":"62","author":"Lee","year":"2005","journal-title":"Am. J. Health Syst. Pharm."},{"key":"2023101912575981500_ref6","doi-asserted-by":"crossref","DOI":"10.1016\/j.preteyeres.2022.101066","article-title":"The genetic basis for adult onset glaucoma, recent advances and future directions","volume":"90","author":"Wang","year":"2022","journal-title":"Prog. Retin. 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