{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T09:22:55Z","timestamp":1790673775610,"version":"4.1.0"},"reference-count":120,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2020,12,24]],"date-time":"2020-12-24T00:00:00Z","timestamp":1608768000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000053","name":"National Eye Institute","doi-asserted-by":"publisher","award":["EY026479"],"award-info":[{"award-number":["EY026479"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007745","name":"Massachusetts Lions Eye Research Fund","doi-asserted-by":"publisher","award":["none"],"award-info":[{"award-number":["none"]}],"id":[{"id":"10.13039\/100007745","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001818","name":"Research to Prevent Blindness","doi-asserted-by":"publisher","award":["none"],"award-info":[{"award-number":["none"]}],"id":[{"id":"10.13039\/100001818","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Evidence is presented herein supporting the potential of the natural homeostatic glycoprotein CLU (clusterin) as a novel therapeutic for the treatment of dry eye. This idea began with the demonstration that matrix metalloproteinase MMP9 is required for damage to the ocular surface in mouse dry eye. Damage was characterized by degradation of OCLN (occludin), a known substrate of MMP9 and a key component of the paracellular barrier. Following up on this finding, a yeast two-hybrid screen was conducted using MMP9 as the bait to identify other proteins involved. CLU emerged as a strong interacting protein that inhibits the enzymatic activity of MMP9. Previously characterized as a molecular chaperone, CLU is expressed prominently by epithelia at fluid-tissue interfaces and secreted into bodily fluids, where it protects cells and tissues against damaging stress. It was demonstrated that CLU also protects the ocular surface in mouse dry eye when applied topically to replace the natural protein depleted from the dysfunctional tears. CLU is similarly depleted from tears in human dry eye. The most novel and interesting finding was that CLU binds selectively to the damaged ocular surface. In this position, CLU protects against epithelial cell death and barrier proteolysis, and dampens the autoimmune response, while the apical epithelial cell layer is renewed. When present at high enough concentration, CLU also blocks staining by vital dyes used clinically to diagnose dry eye. None of the current therapeutics have this combination of properties to \u201cprotect, seal, and heal\u201d. Future work will be directed towards human clinical trials to investigate the therapeutic promise of CLU.<\/jats:p>","DOI":"10.3390\/ijms22010116","type":"journal-article","created":{"date-parts":[[2020,12,24]],"date-time":"2020-12-24T09:02:44Z","timestamp":1608800564000},"page":"116","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Therapeutic Potential of the Molecular Chaperone and Matrix Metalloproteinase Inhibitor Clusterin for Dry Eye"],"prefix":"10.3390","volume":"22","author":[{"given":"M. Elizabeth","family":"Fini","sequence":"first","affiliation":[{"name":"New England Eye Center, Tufts Medical Center and Department of Ophthalmology, Tufts University School of Medicine, Program in Pharmacology &amp; Drug Development, Graduate School of Biomedical Sciences Tufts University, Boston, MA 02111, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinwu","family":"Jeong","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, USC Roski Eye Institute, Keck School of Medicine of USC, University of Southern California, Los Angeles, CA 90089, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark R.","family":"Wilson","sequence":"additional","affiliation":[{"name":"The Illawarra Health and Medical Research Institute, Molecular Horizons and the School of Chemistry and Molecular Bioscience, University of Wollongong, Wollongong, NSW 2522, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,12,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"4391","DOI":"10.1167\/iovs.07-0770","article-title":"The Ocular Surface: The Challenge to Enable and Protect Vision: The Friedenwald lecture","volume":"48","author":"Gipson","year":"2007","journal-title":"Investig. 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