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In the present study, we successfully detected the expression of NHE8 in the ocular surface by PCR and Western blot in human and mouse eyes. Immunohistochemistry staining located NHE8 protein at the plasma membrane of the epithelial cells in the conjunctiva, the cornea, and the lacrimal gland both in human and mouse. We also detected the expression of downregulated-in-adenoma (DRA, a Cl<jats:sup>\u2212<\/jats:sup>\/HCO<jats:sub>3<\/jats:sub><jats:sup>\u2212<\/jats:sup>transporter) in the ocular surface epithelial cells. Using NHE8\u2212\/\u2212 mouse model, we found that loss of NHE8 function resulted in reduced tear production and increased corneal staining. These NHE8\u2212\/\u2212 mice also showed increased expression of TNF-\u03b1 and matrix metalloproteinase 9 (MMP9) genes. The expression of epithelial keratinization marker genes, small proline-rich protein 2h (Sprr2h) and transglutaminase 1 (Tgm1), were also increased in NHE8\u2212\/\u2212 eyes. Furthermore, DRA expression in NHE8\u2212\/\u2212 mice was reduced in the conjunctiva, the cornea, and the lacrimal glands in association with a reduction in conjunctival mucosal pH. Altered ocular surface function and reduced epithelial DRA expression in NHE8\u2212\/\u2212 mice suggest that the role of NHE8 in ocular surface tissue involve in tear production and ocular epithelial protection. This study reveals a potential novel mechanism of dry eye condition involving abnormal NHE8 function.<\/jats:p>","DOI":"10.1152\/ajpcell.00296.2014","type":"journal-article","created":{"date-parts":[[2014,11,7]],"date-time":"2014-11-07T08:50:29Z","timestamp":1415350229000},"page":"C79-C87","source":"Crossref","is-referenced-by-count":17,"title":["Loss of NHE8 expression impairs ocular surface function in mice"],"prefix":"10.1152","volume":"308","author":[{"given":"Hua","family":"Xu","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Steele Children's Research Center, University of Arizona College of Medicine, Tucson, Arizona;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Steele Children's Research Center, University of Arizona College of Medicine, Tucson, Arizona;"},{"name":"Department of Ophthalmology, Shenyang Northern Hospital, Shenyang, People's 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