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The pathogenic factors of dry eye disease (DED) include tear secretion abnormalities, tear film instability and ocular surface inflammation. An effective intervention targeting the pathogenic factors is needed to control this disease. Here we applied \u03b1-Melanocyte-stimulating hormone (\u03b1-MSH) twice a day to the ocular surface of a scopolamine-induced dry eye rat model. The results showed that \u03b1-MSH at different doses ameliorated tear secretion, tear film stability and corneal integrity and corrected overexpression of proinflammatory factors, TNF-\u03b1, IL-1\u03b2 and IFN-\u03b3, in ocular surface of the dry eye rats. Moreover, \u03b1-MSH, at 10<jats:sup>\u22124<\/jats:sup>\u2009\u03bcg\/\u03bcl, maintained corneal morphology, inhibited apoptosis and restored the number and size of conjunctival goblet cells in the dry eye rats. Mechanistically, \u03b1-MSH activated both PKA-CREB and MEK-Erk pathways in the dry eye corneas and conjunctivas; pharmacological blockade of either pathway abolished \u03b1-MSH\u2019s protective effects, suggesting that both pathways are necessary for \u03b1-MSH\u2019s protection under dry eye condition. The peliotropic protective functions and explicit signaling mechanism of \u03b1-MSH warrant translation of the \u03b1-MSH-containing eye drop into a novel and effective intervention to DED.<\/jats:p>","DOI":"10.1038\/srep18619","type":"journal-article","created":{"date-parts":[[2015,12,21]],"date-time":"2015-12-21T13:03:47Z","timestamp":1450703027000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":46,"title":["\u03b1-Melanocyte-stimulating hormone ameliorates ocular surface dysfunctions and lesions in a scopolamine-induced dry eye model via PKA-CREB and MEK-Erk pathways"],"prefix":"10.1038","volume":"5","author":[{"given":"Yusha","family":"Ru","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huijuan","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Du","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhu","family":"Meng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zexia","family":"Dou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xun","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui Hua","family":"Wei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","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":[[2015,12,21]]},"reference":[{"key":"BFsrep18619_CR1","doi-asserted-by":"crossref","unstructured":"The definition and classification of dry eye disease: report of the Definition and Classification Subcommittee of the International Dry Eye WorkShop (2007). 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