Effects of sequential injections of hepatocyte growth factor and insulin-like growth factor-I on adult rabbit extraocular muscle

Abstract

Purpose To determine whether hepatocyte growth factor (HGF) and insulin-like growth factor-I (IGF-I) have synergistic effects in promoting extraocular muscle fiber growth and force generation. Methods A superior rectus muscle of adult rabbits was treated with either a single injection of HGF or sequential injections of HGF followed 1 week later by IGF-I. One week after HGF alone and 1 week after the IGF-I injection, the superior rectus muscles from treated and control orbits were examined for alterations in force generation as well as changes in myofiber size. Results Injection of HGF alone did not result in changes to muscle force, specific tension, or myofiber cross-sectional area; however, it did result in a significant increase in numbers of satellite cells. Sequential injection of HGF and IGF-I resulted in significantly increased force, specific tension, and myofiber cross-sectional areas as well as increased numbers of satellite cells. Conclusions Preinjection with HGF augments the treatment effect of IGF-I. This is likely a result of HGF-induced activation of satellite cells. This synergistic effect should allow a reduction in IGF-I dosing required to produce a given increase in extraocular muscle force generation.

Eye alignment changes caused by sustained GDNF treatment of an extraocular muscle in infant non-human primates

“…If pellets alone caused perturbations in alignment, then contralateral implantation of the placebo pellet would negate the effects of the first pellet, which was not seen. Similarly, in rabbit studies, injections of hepatocyte growth factor (HGF) alone did not cause changes to the muscle physiology or myofiber morphometry, while injections with IGF-1 produced significant changes in muscle function and protein expression, and injection with HGF followed by IGF-1 produced even greater significant changes to myofiber force generation and myofiber mean cross-sectional areas 35 . In our studies in rabbit, we included cases with just saline injections compared to neurotrophic factor injections and found no functional changes in these sham-treated muscles 36 .…”