{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T07:01:33Z","timestamp":1791356493311,"version":"4.3.1"},"reference-count":27,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,1,13]],"date-time":"2021-01-13T00:00:00Z","timestamp":1610496000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,1,13]],"date-time":"2021-01-13T00:00:00Z","timestamp":1610496000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81970769"],"award-info":[{"award-number":["81970769"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>An important mechanism involved in dry eye (DE) is the association between tear hyperosmolarity and inflammation severity. Inflammation in DE might be mediated by the NLRP3 inflammasome, which activated by exposure to reactive oxygen species (ROS). A combination of carboxymethylcellulose (CMC) and \u03b1-melanocyte stimulating hormone (\u03b1-MSH) may influence DE through this mechanism, thus avoiding defects of signal drug. In this study, we assessed whether treatment comprising CMC combined with \u03b1-MSH could ameliorate ocular surface function; we found that it promoted tear secretion, reduced the density of fluorescein sodium staining, enhanced the number of conjunctival goblet cells, and reduced the number of corneal apoptotic cells. Investigation of the underlying mechanism suggested that the synergistic effect of combined treatment alleviated DE inflammation through reduction of ROS level and inhibition of the NLRP3 inflammasome in human corneal epithelial cells. These findings indicate that combined CMC\u2009+\u2009\u03b1-MSH treatment could ameliorate lesions and restore ocular surface function in patients with DE through reduction of ROS level and inhibition of NLRP3 signalling.<\/jats:p>","DOI":"10.1038\/s41598-020-80849-2","type":"journal-article","created":{"date-parts":[[2021,1,13]],"date-time":"2021-01-13T11:15:21Z","timestamp":1610536521000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["A combination of CMC and \u03b1-MSH inhibited ROS activated NLRP3 inflammasome in hyperosmolarity stressed HCECs and scopolamine-induced dry eye rats"],"prefix":"10.1038","volume":"11","author":[{"given":"Ying","family":"Lv","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenchen","family":"Chu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ke","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yusha","family":"Ru","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoxiao","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yichen","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caijie","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaozhen","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,1,13]]},"reference":[{"issue":"1","key":"80849_CR1","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1097\/ICU.0000000000000227","volume":"27","author":"C Sutu","year":"2016","unstructured":"Sutu, C., Fukuoka, H. & Afshari, N. A. Mechanisms and management of dry eye in cataract surgery patients. Curr. Opin. Ophthalmol. 27(1), 24\u201330 (2016).","journal-title":"Curr. Opin. Ophthalmol."},{"issue":"3","key":"80849_CR2","doi-asserted-by":"publisher","first-page":"276","DOI":"10.1016\/j.jtos.2017.05.008","volume":"15","author":"JP Craig","year":"2017","unstructured":"Craig, J. P. et al. Tfos dews ii definition and classification report. Ocul. Surf. 15(3), 276\u2013283 (2017).","journal-title":"Ocul. Surf."},{"issue":"4","key":"80849_CR3","doi-asserted-by":"publisher","first-page":"390","DOI":"10.1136\/bjo.83.4.390","volume":"83","author":"K Tsubota","year":"1999","unstructured":"Tsubota, K. et al. Treatment of dry eye by autologous serum application in sjogren\u2019s syndrome. Br. J. Ophthalmol. 83(4), 390\u2013395 (1999).","journal-title":"Br. J. Ophthalmol."},{"issue":"5","key":"80849_CR4","first-page":"948","volume":"42","author":"G Geerling","year":"2001","unstructured":"Geerling, G., Daniels, J. T., Dart, J. K., Cree, I. A. & Khaw, P. T. Toxicity of natural tear substitutes in a fully defined culture model of human corneal epithelial cells. Invest. Ophthalmol. Vis. Sci. 42(5), 948\u2013956 (2001).","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"issue":"10","key":"80849_CR5","first-page":"2268","volume":"40","author":"T Nishida","year":"1999","unstructured":"Nishida, T. & Taylor, A. W. Specific aqueous humor factors induce activation of regulatory t cells. Invest. Ophthalmol. Vis. Sci. 40(10), 2268\u20132274 (1999).","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"issue":"2","key":"80849_CR6","doi-asserted-by":"publisher","first-page":"179","DOI":"10.3109\/09273948.2015.1092560","volume":"25","author":"CM Clemson","year":"2017","unstructured":"Clemson, C. M., Yost, J. & Taylor, A. W. The role of alpha-msh as a modulator of ocular immunobiology exemplifies mechanistic differences between melanocortins and steroids. Ocul. Immunol. Inflamm. 25(2), 179\u2013189 (2017).","journal-title":"Ocul. Immunol. Inflamm."},{"issue":"13\u201314","key":"80849_CR7","doi-asserted-by":"publisher","first-page":"1883","DOI":"10.1016\/j.intimp.2006.07.032","volume":"6","author":"J Tsang","year":"2006","unstructured":"Tsang, J. et al. In-vitro generation and characterisation of murine cd4+cd25+ regulatory t cells with indirect allospecificity. Int. Immunopharmacol. 6(13\u201314), 1883\u20131888 (2006).","journal-title":"Int. Immunopharmacol."},{"issue":"11","key":"80849_CR8","doi-asserted-by":"publisher","first-page":"840","DOI":"10.1007\/s00417-001-0379-1","volume":"239","author":"N Naveh","year":"2001","unstructured":"Naveh, N. & Marshall, J. Melanocortins are comparable to corticosteroids as inhibitors of traumatic ocular inflammation in rabbits. Graefes Arch. Clin. Exp. Ophthalmol. 239(11), 840\u2013844 (2001).","journal-title":"Graefes Arch. Clin. Exp. Ophthalmol."},{"issue":"9","key":"80849_CR9","doi-asserted-by":"publisher","first-page":"1079","DOI":"10.1016\/j.intimp.2009.05.001","volume":"9","author":"DJ Lee","year":"2009","unstructured":"Lee, D. J., Biros, D. J. & Taylor, A. W. Injection of an alpha-melanocyte stimulating hormone expression plasmid is effective in suppressing experimental autoimmune uveitis. Int. Immunopharmacol. 9(9), 1079\u20131086 (2009).","journal-title":"Int. Immunopharmacol."},{"issue":"4","key":"80849_CR10","first-page":"1407","volume":"36","author":"J Pavan","year":"2012","unstructured":"Pavan, J. et al. Effects of alpha-msh on corneal epithelial lesions in rats. Coll. Antropol. 36(4), 1407\u20131411 (2012).","journal-title":"Coll. Antropol."},{"key":"80849_CR11","doi-asserted-by":"publisher","first-page":"18619","DOI":"10.1038\/srep18619","volume":"5","author":"Y Ru","year":"2015","unstructured":"Ru, Y. et al. Alpha-melanocyte-stimulating hormone ameliorates ocular surface dysfunctions and lesions in a scopolamine-induced dry eye model via pka-creb and mek-erk pathways. Sci. Rep. 5, 18619 (2015).","journal-title":"Sci. Rep."},{"issue":"2 Suppl","key":"80849_CR12","first-page":"S227","volume":"15","author":"LM Lenton","year":"1999","unstructured":"Lenton, L. M. & Albietz, J. M. Effect of carmellose-based artificial tears on the ocular surface in eyes after laser in situ keratomileusis. J. Refract. Surg. 15(2 Suppl), S227-231 (1999).","journal-title":"J. Refract. Surg."},{"key":"80849_CR13","doi-asserted-by":"publisher","first-page":"1651","DOI":"10.1016\/S0886-3350(01)01348-7","volume":"28","author":"JA Ahee","year":"2002","unstructured":"Ahee, J. A., Kaufman, S. C., Samuel, M. A., Bogorad, D. & Wee, C. Decreased incidence of epithelial defects during laser in situ keratomileusis using intraoperative nonpreserved carboxymethylcellulose sodium 0.5% solution. J. Cataract Refract. Surg. 28, 1651\u20131654 (2002).","journal-title":"J. Cataract Refract. Surg."},{"key":"80849_CR14","first-page":"215","volume":"8","author":"JS Lee","year":"2015","unstructured":"Lee, J. S., Lee, S. U., Che, C. Y. & Lee, J. E. Comparison of cytotoxicity and wound healing effect of carboxymethylcellulose and hyaluronic acid on human corneal epithelial cells. Int. J. Ophthalmol. 8, 215\u2013221 (2015).","journal-title":"Int. J. Ophthalmol."},{"issue":"3","key":"80849_CR15","doi-asserted-by":"publisher","first-page":"575","DOI":"10.1016\/j.jtos.2017.05.006","volume":"15","author":"L Jones","year":"2017","unstructured":"Jones, L. et al. Tfos dews ii management and therapy report. Ocul Surf. 15(3), 575\u2013628 (2017).","journal-title":"Ocul Surf."},{"key":"80849_CR16","doi-asserted-by":"crossref","unstructured":"Bron, A. J. et al. Corrigendum to \"tfos dews ii pathophysiology report\" [ocul. Surf. 15 (3), 438\u2013510 (2017)]. Ocul Surf. 17, 842 (2019).","DOI":"10.1016\/j.jtos.2019.08.007"},{"key":"80849_CR17","doi-asserted-by":"publisher","first-page":"452","DOI":"10.1097\/ICO.0b013e318030d259","volume":"26","author":"L Luo","year":"2007","unstructured":"Luo, L., Li, D. Q. & Pflugfelder, S. C. Hyperosmolarity-induced apoptosis in human corneal epithelial cells is mediated by cytochrome c and mapk pathways. Cornea 26, 452\u2013460 (2007).","journal-title":"Cornea"},{"key":"80849_CR18","doi-asserted-by":"publisher","first-page":"6287","DOI":"10.1167\/iovs.13-12081","volume":"54","author":"W Chen","year":"2013","unstructured":"Chen, W. et al. Efficacy of osmoprotectants on prevention and treatment of murine dry eye. Invest. Ophthalmol. Vis. Sci. 54, 6287\u20136297 (2013).","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"issue":"3","key":"80849_CR19","doi-asserted-by":"publisher","first-page":"491","DOI":"10.1038\/eye.2017.241","volume":"32","author":"P Yerramothu","year":"2018","unstructured":"Yerramothu, P., Vijay, A. K. & Willcox, M. D. P. Inflammasomes, the eye and anti-inflammasome therapy. Eye (Lond). 32(3), 491\u2013505 (2018).","journal-title":"Eye (Lond)."},{"key":"80849_CR20","doi-asserted-by":"publisher","first-page":"101093","DOI":"10.1016\/j.redox.2018.101093","volume":"21","author":"Y Dai","year":"2019","unstructured":"Dai, Y. et al. Calcitriol inhibits ros-nlrp3-il-1beta signaling axis via activation of nrf2-antioxidant signaling in hyperosmotic stress stimulated human corneal epithelial cells. Redox Biol. 21, 101093 (2019).","journal-title":"Redox Biol."},{"key":"80849_CR21","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1016\/j.exer.2015.02.013","volume":"134","author":"Q Zheng","year":"2015","unstructured":"Zheng, Q. et al. Reactive oxygen species activated nlrp3 inflammasomes initiate inflammation in hyperosmolarity stressed human corneal epithelial cells and environment-induced dry eye patients. Exp Eye Res. 134, 133\u2013140 (2015).","journal-title":"Exp Eye Res."},{"key":"80849_CR22","doi-asserted-by":"publisher","first-page":"249","DOI":"10.1007\/s11302-017-9556-5","volume":"13","author":"A Guzman-Aranguez","year":"2017","unstructured":"Guzman-Aranguez, A., Perez de Lara, M. J. & Pintor, J. Hyperosmotic stress induces atp release and changes in p2x7 receptor levels in human corneal and conjunctival epithelial cells. Purinergic Signal. 13, 249\u2013258 (2017).","journal-title":"Purinergic Signal."},{"key":"80849_CR23","doi-asserted-by":"publisher","first-page":"923","DOI":"10.1016\/j.immuni.2015.10.009","volume":"43","author":"D Yang","year":"2015","unstructured":"Yang, D., He, Y., Munoz-Planillo, R., Liu, Q. & Nunez, G. Caspase-11 requires the pannexin-1 channel and the purinergic p2x7 pore to mediate pyroptosis and endotoxic shock. Immunity 43, 923\u2013932 (2015).","journal-title":"Immunity"},{"key":"80849_CR24","doi-asserted-by":"publisher","first-page":"657","DOI":"10.2147\/OPTH.S74849","volume":"9","author":"PA Simmons","year":"2015","unstructured":"Simmons, P. A., Carlisle-Wilcox, C. & Vehige, J. G. Comparison of novel lipid-based eye drops with aqueous eye drops for dry eye: A multicenter, randomized controlled trial. Clin. Ophthalmol. 9, 657\u2013664 (2015).","journal-title":"Clin. Ophthalmol."},{"key":"80849_CR25","doi-asserted-by":"publisher","first-page":"1409","DOI":"10.1038\/eye.2017.73","volume":"31","author":"M Labetoulle","year":"2017","unstructured":"Labetoulle, M., Chiambaretta, F., Shirlaw, A., Leaback, R. & Baudouin, C. Osmoprotectants, carboxymethylcellulose and hyaluronic acid multi-ingredient eye drop: A randomised controlled trial in moderate to severe dry eye. Eye (Lond). 31, 1409\u20131416 (2017).","journal-title":"Eye (Lond)."},{"issue":"6","key":"80849_CR26","doi-asserted-by":"publisher","first-page":"857","DOI":"10.1007\/s00417-008-0784-9","volume":"246","author":"S Viau","year":"2008","unstructured":"Viau, S. et al. Time course of ocular surface and lacrimal gland changes in a new scopolamine-induced dry eye model. Graefes Arch. Clin. Exp. Ophthalmol. 246(6), 857\u2013867 (2008).","journal-title":"Graefes Arch. Clin. Exp. Ophthalmol."},{"key":"80849_CR27","first-page":"0222515","volume":"14","author":"X Lu","year":"2019","unstructured":"Lu, X. et al. High-throughput rna-sequencing identifies mesenchymal stem cell-induced immunological signature in a rat model of corneal allograft rejection. PLoS ONE 14, 0222515 (2019).","journal-title":"PLoS ONE"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-80849-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-80849-2","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-80849-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,3]],"date-time":"2022-12-03T02:07:15Z","timestamp":1670033235000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-80849-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,1,13]]},"references-count":27,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["80849"],"URL":"https:\/\/doi.org\/10.1038\/s41598-020-80849-2","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,1,13]]},"assertion":[{"value":"26 April 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 October 2020","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 January 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"1184"}}