ArticleAmerican journal of physiology. Cell physiology2015
Loss of NHE8 expression impairs ocular surface function in mice.
Article in American journal of physiology. Cell physiology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed, 17 citations in OpenAlex.
- The SLC-ome of membrane transport: from molecular discovery to physiology and clinical applications.Physiological reviews · 2026Review
- Ocular Surface Ion Transport and Dry Eye Disease.Current ophthalmology reports · 2022Article
- NHE8 Deficiency Promotes Colitis-Associated Cancer in Mice via Expansion of Lgr5-Expressing Cells.Cellular and molecular gastroenterology and hepatology · 2019Article
- SLC9 Gene Family: Function, Expression, and Regulation.Comprehensive Physiology · 2018Review
- Pathophysiology of Intestinal NaCellular and molecular gastroenterology and hepatology · 2017Article
- Intestinal NHE8 is highly expressed in goblet cells and its expression is subject to TNF-α regulation.American journal of physiology. Gastrointestinal and liver physiology · 2016Article
- Mouse slc9a8 mutants exhibit retinal defects due to retinal pigmented epithelium dysfunction.Investigative ophthalmology & visual science · 2015Article
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
Sodium/hydrogen exchanger (NHE) 8 is expressed at the apical membrane of the epithelial cells and plays important roles in neutral sodium absorption in the gastrointestinal tract and the kidney. It also has an important role in epithelial mucosal protection in the gastric gland and the intestine. Although NHE8 has broad tissue distribution, the precise location and the physiological role of NHE8 in the eye remain unknown. 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(-)/HCO3 (-) transporter) in the ocular surface epithelial cells. Using NHE8-/- mouse model, we found that loss of NHE8 function resulted in reduced tear production and increased corneal staining. These NHE8-/- mice also showed increased expression of TNF-α 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-/- eyes. Furthermore, DRA expression in NHE8-/- 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-/- 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.
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