A CXCR3-Activating Peptide Increases Tear Break Up Time and Corrects Corneal haze in a Rabbit Model of Environmental Dry Eye

Author(s): Alan Wells, Yadong Wang, Hanshuang Shao, Peri Sohnen, Shivalingappa K. Swamynathan

Purpose: Environmentally-triggered dry eye disease (DED) or keratoconjunctivitis sicca (KCS), which constitutes the majority of DED cases, currently is palliatively treated with aqueous replacement solutions that do not target the dysfunction of the mucin and lipid components of tears. We tested whether a peptide that increased goblet cell numbers in a model of scleral chemical injury would also improve tear quality in environmental DED.

Methods: Environmental DED was established by exposing New Zealand white rabbits (8 per group, female) to 20% humidity with rapid air replacement and b.i.d. atropine sulfate eyedrops for 3 weeks prior to test article administration; this continued for the subsequent 3 weeks of testing. Animals were dosed by (A) saline, (B) b.i.d. eyedrop of peptide in saline, (C) b.i.d. eyedrop of peptide in coacervate, or (D) weekly subconjunctival injection of peptide. In vitro, human conjunctival epithelial cells (HCjE) were exposed to TNFa in the presence or absence of peptide to determine inflammatory responsiveness.

Results: The environmental DED was established with both Schirmer and TBUT being reduced at the start of test article; these levels were maintained as low through the testing period. All three treatment regimens increased TBUT approximately 3x to levels greater than prior to desiccation (P < 0.01), with little effect on Schirmer. Corneal haze was present in all eyes after induction, and completely reversed in 36 of 48 eyes across the treatments (P < 0.05). Co-treatment of HCjE with peptide reduced the production of TNFa in response to an inflammatory stimulus.

Conclusions: The treatment of environmental DED/KCS with a peptide that activates CXCR3 improved tear quality and reversed corneal pathology by promoting tear stability and likely dampening the corneal inflammation, while not affecting aqueous volume of the tears.