Results
Title

Calcineurin Inhibitor Voclosporin Preserves Corneal Barrier and Conjunctival Goblet Cells in Experimental Dry Eye.

Authors

Alam, Jehan; de Souza, Rodrigo G.; Yu, Zhiyuan; Stern, Michael E.; de Paiva, Cintia S.; Pflugfelder, Stephen C.

Abstract

Objective: The purpose of this study was to evaluate the potential of voclosporin (VOS) in preventing goblet cell (GC) loss and modulating interferon-gamma (IFN-γ) producing CD4 T cells in the mouse desiccating stress (DS) dry eye model. Methods: Mice were subjected to DS and treated topically with vehicle, VOS, or cyclosporine A as a treatment control. Corneal barrier function was evaluated after 5 and conjunctival GC density after 10 days of desiccation. CD4 T cells were isolated from ocular surface draining lymph nodes of dry eye donor mice and adoptively transferred into immune deficient RAG1-/- mice from which tears and conjunctiva were collected for the evaluation of inflammatory cytokines/chemokines and GC density. Results: Compared to the vehicle-treated group, VOS was significantly better in preserving corneal barrier function and preventing DS-induced conjunctival GC loss. CD4 T cells from VOS treated dry eye donors caused less conjunctival GC loss than vehicle and suppressed expression of IFN-γ signature genes to a similar extent and transforming growth factor-beta to a greater extent than cyclosporine in adoptive transfer recipients. Conclusion: These findings suggest that VOS preserves corneal barrier function and conjunctival GCs and suppresses IFN-γ producing CD4 T cells in experimental dry eye.

Subjects

DRY eye syndromes; ELECTRIC batteries; CALCINEURIN; T cells; LYMPH nodes; CORNEA physiology; BIOLOGICAL models; RESEARCH; IMMUNIZATION; ANIMAL experimentation; RESEARCH methodology; MEDICAL cooperation; EVALUATION research; CYCLOSPORINE; CONJUNCTIVA; COMPARATIVE studies; RESEARCH funding; EPITHELIAL cells; IMMUNOSUPPRESSIVE agents; CORNEA; MICE; PHARMACODYNAMICS

Publication

Journal of Ocular Pharmacology & Therapeutics, 2020, Vol 36, Issue 9, p679

ISSN

1080-7683

Publication type

Academic Journal

DOI

10.1089/jop.2020.0005