{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T01:02:40Z","timestamp":1792803760339,"version":"4.5.0"},"reference-count":69,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2023,12,1]],"date-time":"2023-12-01T00:00:00Z","timestamp":1701388800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Serbian Ministry of Science","award":["451-03-47\/2023-01\/200111"],"award-info":[{"award-number":["451-03-47\/2023-01\/200111"]}]},{"name":"Serbian Ministry of Science","award":["MP01\/18"],"award-info":[{"award-number":["MP01\/18"]}]},{"name":"European Crohn\u2019s and Colitis Organization (ECCO)","award":["451-03-47\/2023-01\/200111"],"award-info":[{"award-number":["451-03-47\/2023-01\/200111"]}],"id":[{"id":"https:\/\/ror.org\/05beaae04","id-type":"ROR","asserted-by":"crossref"}]},{"name":"European Crohn\u2019s and Colitis Organization (ECCO)","award":["MP01\/18"],"award-info":[{"award-number":["MP01\/18"]}],"id":[{"id":"https:\/\/ror.org\/05beaae04","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Faculty of Medical Sciences University of Kragujevac","award":["451-03-47\/2023-01\/200111"],"award-info":[{"award-number":["451-03-47\/2023-01\/200111"]}],"id":[{"id":"https:\/\/ror.org\/04f7vj627","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Faculty of Medical Sciences University of Kragujevac","award":["MP01\/18"],"award-info":[{"award-number":["MP01\/18"]}],"id":[{"id":"https:\/\/ror.org\/04f7vj627","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Dry eye disease (DED) is a multifactorial disorder of the lacrimal system and ocular surface, characterized by a deficiency in the quality and\/or quantity of the tear fluid. The multifactorial nature of DED encompasses a number of interconnected underlying pathologies, including loss of homeostasis, instability and hyperosmolarity of the tears, and the induction and propagation of detrimental inflammatory responses in the eyes, which finally results in the development of neurosensory dysfunction and visual disruption. Dryness, grittiness, scratchiness, discomfort, inflammation, burning, watering, ocular fatigue, pain, and decreased functional visual acuity are common symptoms of DED. Eye dysfunction drastically attenuates patients\u2019 quality of life. Accordingly, a better understanding of the pathogenic processes that regulate the development and progression of DED is crucially important for the establishment of new and more effective DED-related treatment approaches, which would significantly improve the quality of life of DED patients. Since the process of osmoregulation, which guards the ocular surface epithelia and maintains normal vision, is affected when the osmolarity of the tears is greater than that of the epithelial cells, tear hyperosmolarity (THO) is considered an initial, important step in the development, progression, and aggravation of DED. In order to delineate the role of THO in the pathogenesis of DED, in this review article, we summarize current knowledge related to the molecular mechanisms responsible for the development of THO-induced pathological changes in the eyes of DED patients, and we briefly discuss the therapeutic potential of hypo-osmotic eye drops in DED treatment.<\/jats:p>","DOI":"10.3390\/cells12232755","type":"journal-article","created":{"date-parts":[[2023,12,1]],"date-time":"2023-12-01T03:58:02Z","timestamp":1701403082000},"page":"2755","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":59,"title":["The Molecular Mechanisms Responsible for Tear Hyperosmolarity-Induced Pathological Changes in the Eyes of Dry Eye Disease Patients"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5906-9198","authenticated-orcid":false,"given":"Carl Randall","family":"Harrell","sequence":"first","affiliation":[{"name":"Regenerative Processing Plant, LLC, 34176 US Highway 19 N, Palm Harbor, FL 34684, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa","family":"Feulner","sequence":"additional","affiliation":[{"name":"Advanced Eye Care & Aesthetics, 104 Plumtree Rd Suite 107, Bel Air, MD 21015, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentin","family":"Djonov","sequence":"additional","affiliation":[{"name":"Institute of Anatomy, University of Bern, Baltzerstrasse 2, 3012 Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7474-7495","authenticated-orcid":false,"given":"Dragica","family":"Pavlovic","sequence":"additional","affiliation":[{"name":"Departments of Genetics and Microbiology and Immunology, Center for Harm Reduction of Biological and Chemical Hazards, Faculty of Medical Sciences, University of Kragujevac, 69 Svetozar Markovic Street, 34000 Kragujevac, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5948-9902","authenticated-orcid":false,"given":"Vladislav","family":"Volarevic","sequence":"additional","affiliation":[{"name":"Departments of Genetics and Microbiology and Immunology, Center for Harm Reduction of Biological and Chemical Hazards, Faculty of Medical Sciences, University of Kragujevac, 69 Svetozar Markovic Street, 34000 Kragujevac, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,12,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1016\/j.jtos.2017.05.008","article-title":"TFOS DEWS II Definition and Classification Report","volume":"15","author":"Craig","year":"2017","journal-title":"Ocul. 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