Evaluation of novel YP-P10 Peptide in animal models of inflammatory dry eye disease

Abstract

Purpose : This study is aimed to investigate the efficacy of YP-P10 Peptide in several animal models of dry eye disease

Methods : Sprague-Dawley rats were subjected to extraorbital lacrimal gland excision (ELGE) or sham surgery. Seven days after surgery, animals were dosed with Topical ocular YP-P10 Peptide (0.1, 0.3, 1 & 3%) or vehicle BID 14 days. Corneal staining using NEI scale was observed biomicroscopically after instillation of 1% fluorescein. C57BL/6J mice were subjected to desiccating stress (<30% relative humidity) and cholinergic blockage for 1 day (DS). Mice received topical ocular YP-P10 Peptide (0.3, 1 or 3%) or vehicle BID 3 days before starting DS and continued during DS. Additional controls were naïve mice not subjected to DS, and DS mice dosed with ocular dexamethasone sodium phosphate. Tears were collected using capillary tubes and inflammatory mediators were measured using Luminex immunoassay. Cornea and conjunctiva were excised and lysed in RNA lysis buffer and subjected to qPCR for a panel of inflammatory markers that have been implicated in dry eye.

Results : Rats: A statistically significant (p<0.001) increase of the fluorescein-stained cornea score based on the NEI scoring scale was observed on the eyes of the ELGE group compared to the SHAM group. Treatment with YP-P10 Peptide reduced corneal damage. Mice: DS increased mRNA levels of G-csf in cornea and Il6, Ccl20, Mmp3, Tnf in conjunctiva. A dose-dependent decrease in several inflammatory mediators associated with dry eye (Il1b, Ccl5 and Cxcl10) was observed in the cornea and conjunctiva, reaching statistical significance compared to vehicle and showing activity similar to dexamethasone in the conjunctiva. This was accompanied by significant decrease in CCL5 and an increase in IL-10 in tear fluid of YP-P10 Peptide treated animals.

Conclusions : Topical ocular YP-P10 Peptide reduced corneal epithelial disease in a rat ELGE dry model and several inflammatory mediators in DS-induced dry eye disease in mice. This anti-inflammatory effect suggests that YP-P10 Peptide might have efficacy in the treatment of dry eye induced ocular surface inflammation.

This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.