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Stephen P. Christiansen, Linda K. McLoon; Hepatocyte Growth Factor Augments the Effect of Insulin Growth Factor-1 on Extraocular Muscle Force Generation in Rabbits. Invest. Ophthalmol. Vis. Sci. 2011;52(14):2076.
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Hepatocyte growth factor (HGF) stimulates mitogenesis and plays a central role in tissue regeneration. In skeletal muscle, HGF activates quiescent satellite cells. Previously, we have shown that insulin growth factor-1 (IGF1) increases myofiber cross-sectional area and force generation in extraocular muscle (EOM). In this study, we test the effect of sequential injections of HGF and IGF1 on EOM morphogenesis and force generation.
Adult rabbits received injections into one superior rectus muscle of either HGF, 2.5µg, alone, or HGF, 2.5µg, followed one week later by 5µg IGF1. Saline was injected into the contralateral superior rectus muscle as a control. One week after final injection, the rabbits were euthanized, and both superior rectus muscles were removed for in-vitro physiological force assessment and muscle morphometry.
HGF, 2.5µg, alone resulted in no significant increase in force generation of the treated muscles compared to saline only. In earlier studies, we found that IGF1 treatment increases EOM force generation by 24% at tetanic stimulation frequencies. In the current study, pretreatment with HGF, 2.5µg, one week prior to IGF1 injection resulted in a > 40% increase in EOM force generation. The treatment effect was less robust when pre-treated with HGF, 1.0µg.
Pre-injection of HGF significantly increases force generation in IGF1-treated EOM. These results suggest that exogenously-induced satellite cell activation in EOM raises the potential for myofiber growth induced by IGF1, the result of which is greater motive force. Previous work in our laboratory has shown that naturally-occurring growth factors and muscle signaling factors can increase or decrease the strength of EOM, and may be useful in the treatment of patients with strabismus. This study suggests that co-administration of growth factors may augment treatment effects, potentially increasing effectiveness for patients with larger angles of ocular misalignment.
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