Effect of TMAO, a Gut-Bacteria Metabolite, on Dry Eye in a Rat Model

Curr Eye Res. 2019 Jun;44(6):651-656. doi: 10.1080/02713683.2019.1574834. Epub 2019 Apr 18.

Abstract

PURPOSE Trimethylamine oxide (TMAO) is an osmolyte used by saltwater animals to protect their cells from hyperosmotic environment. Here, we studied if TMAO may exert beneficial effect in dry eye disease (DED) which results from hyperosmotic tear film. MATERIALS AND METHODS Female, 12-week-old Sprague-Dawley rats underwent either removal of extra- and infraorbital lacrimal glands (dry eye group) or sham surgery (sham group). A 1-week topical treatment with either 0.9% NaCl (control) or 1% TMAO in 0.9% NaCl solution was started 4 weeks after the surgery. Fluorescein score (FS), blink rate (BR), and histological picture of cornea were assessed. RESULTS At baseline, corneas did not stain with fluorescein and there was no difference between the groups in BR. There was a significant increase in FS and BR after the removal of lacrimal glands (p < 0.0001 and p = 0.0003, respectively). Accordingly, the dry eye group showed significantly higher FS and BR than the sham group (p = 0.0003 and p = 0.0005, respectively). Treatment with TMAO but not with 0.9% NaCl significantly reduced FS and BR (p = 0.01 and p = 0.005, respectively); however, FS and BR did not return to baseline (p = 0.0045 and p = 0.0065, respectively). In comparison to the control group, treatment with TMAO did not affect epithelial thickness or the number of layers of epithelium layers. CONCLUSIONS We have found that in a rat model of DED, the topical treatment with TMAO improves clinical picture, however does not lead to the evident histopathological recovery.

Keywords: Dry eye; TMAO; cornea; gut-bacteria metabolite; tear film.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Ophthalmic
  • Animals
  • Blinking / physiology
  • Disease Models, Animal*
  • Dry Eye Syndromes / drug therapy*
  • Dry Eye Syndromes / metabolism
  • Female
  • Fluorescein / metabolism
  • Methylamines / therapeutic use*
  • Ophthalmic Solutions
  • Oxidants / therapeutic use*
  • Rats
  • Rats, Sprague-Dawley
  • Staining and Labeling

Substances

  • Methylamines
  • Ophthalmic Solutions
  • Oxidants
  • trimethyloxamine
  • Fluorescein