Topical treatment with an engineered fibroblast growth factor 1 (TTHX1114) decreased inflammatory macrophages in the cornea associated with reduced corneal keratopathy in a mouse model of primary ocular herpes

Abstract

Purpose : To evaluate preclinical efficacy of an engineered Fibroblast growth factor 1 (eFGF-1), designated as TTHX1114, on severity of corneal keratopathy using a mouse model of primary ocular herpes infection. TTHX1114 is known for an enhanced ability to stimulate proliferation of corneal epithelial cells and tissue repair. We determined the effect of TTHX1114 treatment on the quality and the quantity of immune cells that infiltrate the mouse cornea during primary herpetic keratitis.

Methods : The efficacy of two different doses of TTHX1114 (25 and 400ng/ml) were tested against corneal keratopathy in C57/B6 mice following corneal infection with 1x10⁵, 5x10⁵, or 1x10⁶pfu of HSV-1 virus (strain McKrae). Starting day one post-infection (PI) and for 28 days, mice received TTHX1114 twice daily at 8 hrs interval. The severity of primary herpetic stromal keratitis and blepharitis were monitored on days on days 2, 5, 7, 10 and 28 PI. HSV-1 replication in cornea was determined by viral plaque assays in infected eye swabs at 2, 5, 7 & 10 PI. Corneas were harvested on day 7 PI and the quality and the quantity of immune cells that infiltrate were determined by FACS. On day 14 PI, whole corneas mounts were immune-stained for CD31, LYVE-1 markers of lymphangiogenesis.

Results : Compared to HSV-1 infected and non-treated mice, the infected and TTHX1114 treated mice showed: (i) an overall resistance to disease and death; (ii) a significant decrease in primary herpetic stromal keratitis (at days 5, 14 and 21 PI) and blepharitis (at days 7 and 14 PI); and (iii) a significant decrease in corneal inflammatory macrophages. However,TTHX1114 treatment did not affect the number and function of cornea-resident T cells nor virus corneal replication.

Conclusions : Topical corneal treatment with the engineered fibroblast growth factor 1 (TTHX1114) decreased inflammatory macrophages in the cornea associated with reduced corneal keratopathy in a mouse model of primary ocular herpes.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.