Fibroblast growth factor 1 in ocular tissue repair: engineered variants and translational challenges

Fibroblast growth factor 1 (FGF1) is a paracrine growth factor that contributes to tissue maintenance, repair after injury and cellular responses to stress. Its presence has been documented in the cornea, lens, retina and vitreous body. Distribution within the eye, however, does not imply an equivalent role in every ocular disorder. Research is furthest advanced in corneal endothelial repair: engineered FGF1 variants have been tested in organ culture and animal models, and TTHX1114/NM141 has reached early-phase clinical evaluation for corneal endothelial disease. Studies of inflammatory ocular-surface injury report protective effects of the engineered FGF1 variant TTHX1114. A separate group of experiments has examined native or activity-modified FGF1 in diabetes-associated retinal and retinal pigment epithelial (RPE) dysfunction. In diabetic retinal/RPE models, FGF1-related interventions reduced oxidative stress, inflammation and endoplasmic reticulum stress and enhanced autophagic responses. Work on non-diabetic retinal degeneration, lens oxidative stress, proliferative vitreoretinopathy, intraocular tumors, glaucoma, myopia and age-related macular degeneration is much less developed; it is observational in several of these settings and cautionary in others. This review examines the distribution of FGF1 in the eye, evaluates the evidence by disease, and considers factors relevant to FGF1-based treatment. Native FGF1 is distinguished from TTHX1114, TTHX1001, FGF1ΔHBS and other engineered variants, with particular attention to molecular design, metabolic activity, delivery and local exposure. The literature does not support a general reparative role for FGF1 throughout the eye. Whether a particular FGF1 molecule is useful will depend on the tissue and disease stage being treated, the exposure achieved and the safety issues specific to that indication.