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bioRxiv · 10.1101/2022.12.07.519513

A CXCR3-activating peptide increases Tear Break Up Time and corrects corneal haze in a rabbit model of environmental dry eye

Wells, A.·Wang, Y.·Shao, H.·Sohnen, P. C.·Swamynathan, S. K.
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Abstract

PurposeEnvironmentally-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. Herein, 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. MethodsEnvironmental 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. ResultsThe environmental DED was established with both Schirmer and TBUT being reduced by from baseline 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, with little effect on Schirmer. Corneal haze was present in all eyes after induction, and largely cleared up by all three treatments. End of study enucleation of the eye did not show any changes in goblet cells numbers, which remained high throughout the induction and treatment. ConclusionsThe treatment of environmental DED/KCS with a peptide that activates CXCR3 improved tear quality and reversed corneal pathology by promoting tear stability, while not affecting aqueous volume of the tears.

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Wells, A., Wang, Y., Shao, H., Sohnen, P. C., Swamynathan, S. K.. 2022-12-11. A CXCR3-activating peptide increases Tear Break Up Time and corrects corneal haze in a rabbit model of environmental dry eye. https://doi.org/10.1101/2022.12.07.519513

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