bFGF alleviated dry eye disease by modulating inflammatory response and promoting healing process both in vitro and in vivo

Abstract

Purpose : Dry eye disease is a multifactorial disease accompanied by ocular damage. Basic fibroblast growth factor (bFGF) plays an essential role in wound healing, however, its role in dry eye induced ocular damage remains controversial. In this study, we elucidated cellular and molecular major markers of eye inflammation after the use of bFGF in preclinical settings.

Methods : We established in vitro inflammatory model by stimulation of IFN-γ and TNF-α in human corneal epithelial cell (HCEC) and conjunctival epithelial cell (HconEpic). We observed cellular responses, including cell viability, migration, and secretion of cytokines w/o bFGF. In vivo model was established by scopolamine-stimulation in C57BL/6J mouse. bFGF was applied and sodium hyaluronate eye-drop was used as positive control. Corneal damage was evaluated by fluorescein staining. Cytokines and mucus were assayed with ELISA and IHC staining.

Results : bFGF promotes proliferation and migration of HCEC and HconEpic. Under low-dose IFN-γ and TNF-α induced inflammation, bFGF effectively protected cells from death. We have noticed that IL-1α, IL-1β, IL-6 and MMP9 by HCEC, IL-6 and MMP9 by HconEpic were upregulated upon IFN-γ and TNF-α stimulation. bFGF downregulated the level of IL-1α, IL-1β, IL-6 and MMP9 in HCEC. A slight inhibitory effect on the expression of IL-6 by bFGF was observed in HconEpic. Regarding results from cytokine studies, we obtained consistent results from in vivo study. bFGF also showed therapeutic effect on dry eye as evidenced by increased tear secretion, attenuated fluorescein staining of corneas, decreased corneal matrix swelling and fewer number of vessels around conjunctiva. Interestingly, sodium hyaluronate showed no effect on mucus secretion, while bFGF obviously improved the mucus to a normal level.

Conclusions : bFGF showed protective effects on ocular surface epithelial cells in moderate inflammation by promoting cell proliferation, migration and regulating cytokine production. bFGF attenuated mouse dry eye induced ocular damage and increased mucus secretion. All evidence indicated that bFGF could be a prospective approach for the treatment of dry eye, at least in non-severe dry eye disease.

This is a 2021 ARVO Annual Meeting abstract.

 

bFGF modulated proliferation (A) and inflammatory response in HCEC and HConEpic (B & C)

 

bFGF alleviated damage of ocular tissue and inflammation (A & B), improved mucus secretion in mouse dry eye (C & D)