Loss of NHE8 expression impairs ocular surface function in mice

Area of Science:

• Ophthalmology
• Physiology
• Molecular Biology

Background:

• Sodium/hydrogen exchanger (NHE) 8 is vital for sodium absorption and mucosal protection in the GI tract and kidneys.
• The specific role and location of NHE8 in the eye were previously unknown.

Purpose of the Study:

• To investigate the expression and function of NHE8 in the ocular surface.
• To determine the role of NHE8 in tear production, ocular surface integrity, and dry eye disease.

Main Methods:

• PCR and Western blot to detect NHE8 expression in human and mouse eyes.
• Immunohistochemistry to localize NHE8 protein in ocular tissues.
• Analysis of NHE8 knockout (NHE8-/-) mouse models for physiological and molecular changes.

Main Results:

• NHE8 is expressed on the plasma membrane of conjunctival, corneal, and lacrimal gland epithelial cells in humans and mice.
• NHE8-/- mice exhibited reduced tear production, increased corneal staining, and elevated TNF-α and MMP9 gene expression.
• Loss of NHE8 function correlated with decreased DRA expression, reduced conjunctival pH, and increased keratinization markers.

Conclusions:

• NHE8 plays a significant role in maintaining ocular surface function, including tear production and epithelial protection.
• Altered NHE8 function may contribute to dry eye conditions through impaired DRA expression and mucosal pH.
• This study identifies a novel mechanism involving NHE8 in ocular surface homeostasis and dry eye pathogenesis.