{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T21:55:35Z","timestamp":1776808535233,"version":"3.51.2"},"reference-count":51,"publisher":"The Company of Biologists","license":[{"start":{"date-parts":[[2021,5,18]],"date-time":"2021-05-18T00:00:00Z","timestamp":1621296000000},"content-version":"am","delay-in-days":503,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["EY022891 (KSN)"],"award-info":[{"award-number":["EY022891 (KSN)"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001818","name":"Research to Prevent Blindness","doi-asserted-by":"publisher","award":["Unrestricted grant (UCSF, Ophthalmology)"],"award-info":[{"award-number":["Unrestricted grant (UCSF, Ophthalmology)"]}],"id":[{"id":"10.13039\/100001818","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001209","name":"Knights Templar Eye Foundation","doi-asserted-by":"publisher","award":["Career Starter Award (SP)"],"award-info":[{"award-number":["Career Starter Award (SP)"]}],"id":[{"id":"10.13039\/100001209","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000011","name":"Howard Hughes Medical Institute","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100000011","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>Glaucoma is a leading cause of blindness affecting up to 70 million people worldwide. High intraocular pressure (IOP) is a major risk factor for glaucoma. Inefficient aqueous humor (AqH) outflow resulting from structural or functional alterations in ocular drainage tissues are well established to cause high IOP, but the genes and pathways involved are poorly understood. We previously demonstrated that mutations in the gene encoding the serine protease PRSS56 induces ocular angle-closure and high IOP in mice and identified reduced ocular axial length as a potential contributing factor. Here we show that Prss56\u2008\u2212\/- mice also exhibits an abnormal iridocorneal angle configuration characterized by a posterior shift of ocular drainage structures relative to the ciliary body and iris. Notably, we show that retina-derived PRSS56 is required between postnatal days 13 and 18 for proper iridocorneal configuration and that abnormal positioning of the ocular drainage tissues is not dependent on ocular size reduction in Prss56\u2212\/- mice. Furthermore, we demonstrate that the genetic context modulates the severity of IOP elevation in Prss56 mutant mice and describe a progressive degeneration of ocular drainage tissues that likely contributes to the exacerbation of the high IOP phenotype observed on the C3H\/HeJ genetic background. Finally, we identified five rare PRSS56 variants associated with human primary congenital glaucoma, a condition characterized by abnormal development of the ocular drainage structures. Collectively, our findings point to a role for PRSS56 in the development and maintenance of ocular drainage tissues and IOP homeostasis, and provide new insights into glaucoma pathogenesis.<\/jats:p>","DOI":"10.1242\/dmm.042853","type":"journal-article","created":{"date-parts":[[2020,3,9]],"date-time":"2020-03-09T23:15:13Z","timestamp":1583795713000},"source":"Crossref","is-referenced-by-count":18,"title":["Loss of PRSS56 function leads to ocular angle defects and increased susceptibility to high intraocular pressure"],"prefix":"10.1242","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2134-2240","authenticated-orcid":false,"given":"Cassandre","family":"Labelle-Dumais","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, University of California, San Francisco, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Goutham","family":"Pyatla","sequence":"additional","affiliation":[{"name":"Brien Holden Eye Research Centre, L V Prasad Eye Institute, Hyderabad, India"},{"name":"Manipal Academy of Higher Education, Manipal, Karnataka, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8566-0600","authenticated-orcid":false,"given":"Seyyedhassan","family":"Paylakhi","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, University of California, San Francisco, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicholas G.","family":"Tolman","sequence":"additional","affiliation":[{"name":"Howard Hughes Medical Institute, The Jackson Laboratory, Bar Harbor, ME, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Syed","family":"Hameed","sequence":"additional","affiliation":[{"name":"Brien Holden Eye Research Centre, L V Prasad Eye Institute, Hyderabad, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yusef","family":"Seymens","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, University of California, San Francisco, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eric","family":"Dang","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, University of California, San Francisco, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anil K.","family":"Mandal","sequence":"additional","affiliation":[{"name":"Jasti V. 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