{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T17:18:43Z","timestamp":1782321523102,"version":"3.54.5"},"reference-count":46,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2024,5,16]],"date-time":"2024-05-16T00:00:00Z","timestamp":1715817600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2024,5,31]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Singleton\u2013Merten syndrome (SMS) is a rare immunogenetic disorder affecting multiple systems, characterized by dental dysplasia, aortic calcification, glaucoma, skeletal abnormalities, and psoriasis. Glaucoma, a key feature of both classical and atypical SMS, remains poorly understood in terms of its molecular mechanism caused by DDX58 mutation. This study presented a novel DDX58 variant (c.1649A&gt;C [p.Asp550Ala]) in a family with childhood glaucoma. Functional analysis showed that DDX58 variant caused an increase in IFN\u2010stimulated gene expression and high IFN\u2010\u03b2\u2010based type\u2010I IFN. As the trabecular meshwork (TM) is responsible for controlling intraocular pressure (IOP), we examine the effect of IFN\u2010\u03b2 on TM cells. Our study is the first to demonstrate that IFN\u2010\u03b2 significantly reduced TM cell viability and function by activating autophagy. In addition, anterior chamber injection of IFN\u2010\u03b2 remarkably increased IOP level in mice, which can be attenuated by treatments with autophagy inhibitor chloroquine. To uncover the specific mechanism underlying IFN\u2010\u03b2\u2010induced autophagy in TM cells, we performed microarray analysis in IFN\u2010\u03b2\u2010treated and DDX58 p.Asp550Ala TM cells. It showed that RSAD2 is necessary for IFN\u2010\u03b2\u2010induced autophagy. Knockdown of RSAD2 by siRNA significantly decreased autophagy flux induced by IFN\u2010\u03b2. Our findings suggest that DDX58 mutation leads to the overproduction of IFN\u2010\u03b2, which elevates IOP by modulating autophagy through RSAD2 in\u00a0TM cells.<\/jats:p>","DOI":"10.1096\/fj.202302265rr","type":"journal-article","created":{"date-parts":[[2024,5,16]],"date-time":"2024-05-16T07:05:36Z","timestamp":1715843136000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["<scp>\n                      <i>DDX58<\/i>\n                    <\/scp>\n                    variant triggers\n                    <scp>IFN<\/scp>\n                    \u2010\u03b2\u2010induced autophagy in trabecular meshwork and influences intraocular pressure"],"prefix":"10.1096","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-4153-7152","authenticated-orcid":false,"given":"Xinting","family":"Huang","sequence":"first","affiliation":[{"name":"Department of Ophthalmology The Second Xiangya Hospital of Central South 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