title: α-Melanocyte-stimulating hormone ameliorates ocular surface dysfunctions and lesions in a scopolamine-induced dry eye model via PKA-CREB and MEK-Erk pathways.
abstract: Dry eye is a highly prevalent, chronic, and multifactorial disease that compromises quality of life and generates socioeconomic burdens. 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 α-Melanocyte-stimulating hormone (α-MSH) twice a day to the ocular surface of a scopolamine-induced dry eye rat model. The results showed that α-MSH at different doses ameliorated tear secretion, tear film stability, and corneal integrity, and corrected overexpression of proinflammatory factors, TNF-α, IL-1β, and IFN-γ, in ocular surface of the dry eye rats. Moreover, α-MSH, at 10(-4) μg/μl, maintained corneal morphology, inhibited apoptosis, and restored the number and size of conjunctival goblet cells in the dry eye rats. Mechanistically, α-MSH activated both PKA-CREB and MEK-Erk pathways in the dry eye corneas and conjunctivas; pharmacological blockade of either pathway abolished α-MSH's protective effects, suggesting that both pathways are necessary for α-MSH's protection under dry eye condition. The peliotropic protective functions and explicit signaling mechanism of α-MSH warrant translation of the α-MSH-containing eye drop into a novel and effective intervention to DED.
authors.affiliation: Tianjin Medical University Eye Hospital, Tianjin Medical University Eye Institute, College of Optometry and Ophthalmology, Tianjin Medical University, Tianjin, 300384, China.
authors.forename: Yusha
authors.initials: Y
authors.lastname: Ru
authors.affiliation: Tianjin Medical University Eye Hospital, Tianjin Medical University Eye Institute, College of Optometry and Ophthalmology, Tianjin Medical University, Tianjin, 300384, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Tianjin Medical University Eye Hospital, Tianjin Medical University Eye Institute, College of Optometry and Ophthalmology, Tianjin Medical University, Tianjin, 300384, China.
authors.forename: Huijuan
authors.initials: H
authors.lastname: Liu
authors.affiliation: Tianjin Medical University Eye Hospital, Tianjin Medical University Eye Institute, College of Optometry and Ophthalmology, Tianjin Medical University, Tianjin, 300384, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Du
authors.affiliation: Tianjin Medical University Eye Hospital, Tianjin Medical University Eye Institute, College of Optometry and Ophthalmology, Tianjin Medical University, Tianjin, 300384, China.
authors.forename: Zhu
authors.initials: Z
authors.lastname: Meng
authors.affiliation: Tianjin Medical University Eye Hospital, Tianjin Medical University Eye Institute, College of Optometry and Ophthalmology, Tianjin Medical University, Tianjin, 300384, China.
authors.forename: Zexia
authors.initials: Z
authors.lastname: Dou
authors.affiliation: Tianjin Medical University Eye Hospital, Tianjin Medical University Eye Institute, College of Optometry and Ophthalmology, Tianjin Medical University, Tianjin, 300384, China.
authors.forename: Xun
authors.initials: X
authors.lastname: Liu
authors.affiliation: Tianjin Medical University Eye Hospital, Tianjin Medical University Eye Institute, College of Optometry and Ophthalmology, Tianjin Medical University, Tianjin, 300384, China.
authors.forename: Rui Hua
authors.initials: RH
authors.lastname: Wei
authors.affiliation: Tianjin Medical University Eye Hospital, Tianjin Medical University Eye Institute, College of Optometry and Ophthalmology, Tianjin Medical University, Tianjin, 300384, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Tianjin Medical University Eye Hospital, Tianjin Medical University Eye Institute, College of Optometry and Ophthalmology, Tianjin Medical University, Tianjin, 300384, China.
authors.forename: Shaozhen
authors.initials: S
authors.lastname: Zhao
mesh_terms: D000818:Animals; D003228:Conjunctiva / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D003315:Cornea / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D015352:Dry Eye Syndromes / Q000139:chemically induced / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D006801:Humans; D020930:MAP Kinase Kinase Kinases / Q000235:genetics; D020935:MAP Kinase Signaling System / Q000235:genetics; D008297:Male; D051381:Rats; D012601:Scopolamine / Q000633:toxicity; D013666:Tears / Q000187:drug effects / Q000378:metabolism*; D000521:alpha-MSH / Q000008:administration & dosage* / Q000378:metabolism
chemical_list: D000521:alpha-MSH; D012601:Scopolamine; D020930:MAP Kinase Kinase Kinases