Effect of Fibroblast Growth Factor 2 on Extraocular Muscle Structure and Function

PURPOSE: Mutations in the fibroblast growth factor (FGF) receptor can result in strabismus, but little is known about how FGFs affect extraocular muscle structure and function. These were assessed after short-term and long-term exposure to exogenously applied FGF2 to determine the effect of enhanced signaling. METHODS: One superior rectus muscle of adult rabbits received either a series of three injections of 500 ng, 1 µg, or 5 µg FGF2 and examined after 1 week, or received sustained treatment with FGF2 and examined after 1, 2, or 3 months. Muscles were assessed for alterations in force generation, myofiber size, and satellite cell number after each treatment. RESULTS: One week after the 5 µg FGF2 injections, treated muscles showed significantly increased force generation compared with naïve controls, which correlated with increased myofiber cross-sectional areas and Pax7-positive satellite cells. In contrast, 3 months of sustained FGF2 treatment resulted in decreased force generation, which correlated with decreased myofiber size and decreased satellite cells compared with naïve control and the untreated contralateral side. CONCLUSIONS: FGF2 had distinctly different effects when short-term and long-term treatments were compared. The decreased size and ability to generate force correlated with decreased myofiber areas seen in individuals with Apert syndrome, where there is sustained activation of FGF signaling. Knowing more about signaling pathways critical for extraocular muscle function, development, and disease will pave the way for improved treatment options for strabismus patients with FGF abnormalities in craniofacial disease, which also may be applicable to other strabismus patients.