Modulation of ocular surface desiccation in a murine model by histatin-5 application. Ocul Surf 2023 Jan;27:30-37
Date
12/14/2022Pubmed ID
36513277Pubmed Central ID
PMC10355159DOI
10.1016/j.jtos.2022.12.004Scopus ID
2-s2.0-85145753201 (requires institutional sign-in at Scopus site) 6 CitationsAbstract
PURPOSE: To determine the efficacy of Histatin-5 (Hst5) peptide treatment in ameliorating dry eye disease (DED) phenotype in an in-vivo mouse model of scopolamine and desiccating stress (SDS) dry eye.
METHODS: SDS was induced in female C57BL/6 mice by subcutaneous injections of scopolamine hydrobromide and exposure to low relative humidity and forced air draft for five days. Mouse eyes were topically treated with synthetic Hst5 peptide or balanced salt solution (BSS) twice a day for four days. Control mice were not exposed to SDS induction and did not receive any treatments. Oregon green dextran (OGD) staining was used to evaluate corneal permeability. Histologically, staining with periodic acid schiff (PAS), immunohistochemistry (IHC) and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), were used to quantify the number of goblet cells (GC), CD45+ immune cells and apoptotic cells respectively in formalin fixed paraffin embedded (FFPE) mouse whole eye sections.
RESULTS: Compared to treatment with BSS, Hst5 treatment significantly lowered corneal epithelial permeability, prevented conjunctival epithelial GC loss, decreased conjunctival CD45+ immune cell infiltration and reduced conjunctival epithelial cell apoptosis.
CONCLUSIONS: Hst5 peptide topical treatment significantly improves the clinical parameters observed in SDS experimental model of DED. This is the first report of the efficacy of Hst5 treatment of dry eye phenotype, and potential novel treatment for DED in the clinic. Hst5 represents a new class of efficacious therapeutic agents, demonstrating pro-epithelial and anti-inflammatory activities at the ocular surface.
Author List
Ali M, Shah D, Coursey TG, Lee SM, Balasubramaniam A, Yadavalli T, Edward D, Son KN, Shukla D, Aakalu VKAuthor
Vinay Kumar Aakalu MPH, MD Chair, Professor in the Ophthalmology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsConjunctiva
Desiccation
Disease Models, Animal
Dry Eye Syndromes
Female
Histatins
Mice
Mice, Inbred C57BL
