Calcineurin Inhibitor Voclosporin Preserves Corneal Barrier and Conjunctival Goblet Cells in Experimental Dry Eye.
J Ocul Pharmacol Ther
; 36(9): 679-685, 2020 11.
Article
in En
| MEDLINE
| ID: mdl-32721249
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.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Dry Eye Syndromes
/
Cyclosporine
/
Cornea
/
Goblet Cells
/
Disease Models, Animal
/
Calcineurin Inhibitors
Type of study:
Prognostic_studies
Limits:
Animals
Language:
En
Journal:
J Ocul Pharmacol Ther
Journal subject:
FARMACOLOGIA
/
OFTALMOLOGIA
/
TERAPEUTICA
Year:
2020
Document type:
Article
Affiliation country:
United States