Increasing extraocular muscle strength with insulin-like growth factor II

PURPOSE. Botulinum toxin type A and, more recently, the immunotoxin ricin-mAb35 have been effective as means of pharmacologically weakening the extraocular muscle. However, currently there are no drug treatments to strengthen an underacting extraocular muscle. In limb muscle, treatment with insulin-like growth factor causes myofiber hypertrophy. In this study, the short-term effects of insulin-like growth factor II (IGF-II) on extraocular muscle morphometry and force generation were examined. METHODS. One superior rectus muscle in normal adult rabbits received a single injection of 10 μg IGF-II, and the contralateral muscle received an injection of saline only. One week after injection, muscle morphology and muscle force were compared between the IGF-treated and control muscles. RESULTS. In the treated muscle, there was no significant change in the mean cross-sectional area of myofibers compared with the control. However, there was an increase in the heterogeneity of myofiber cross-sectional area, with increases in both small and very large myofibers. Mean single-twitch force generation was 0.48 ± 0.12 mN/cm ³ compared with 0.27 ± 0.04 mN/cm³ (P = 0.0473) in control samples. Mean tetanic force generation was increased significantly at all stimulation frequencies. Treatment had no effect on muscle fatigability. CONCLUSIONS. Extraocular muscle is very responsive to direct injection of IGF-II. Although no difference was seen in mean myofiber cross-sectional area, overall there was sufficient alteration in myofiber heterogeneity to result in increased force generation. If a sustained treatment effect can be achieved with IGF-II and, potentially, other growth factors, the pharmacological treatment of strabismus could be advanced by simultaneous injection of agonist-antagonist pairs with agents that weaken and strengthen the treated extraocular muscle.