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S.P. Christiansen, S.T. Grandt, L.K. McLoon; Effect of Insulin Growth Factor–I on Force Generation in Adult Extraocular Muscles of Rabbits . Invest. Ophthalmol. Vis. Sci. 2005;46(13):5723.
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Purpose: Future pharmacological treatment of strabismus may be optimized if drugs that augment extraocular muscle (eom) strength can be developed, especially if used in conjunction with agents such as BoTox or ricin–MAb35 to weaken the antagonist. We have previously shown that direct eom injection with IGF–II results in significant but short–term increases in eom force generation. The purpose of this study is to examine the morphometric and physiological effects of IGF–I injection in eom. Methods: The superior rectus muscles of normal adult rabbits were exposed and a single injection of IGF–I (10ng/µl) was injected into one muscle. The contralateral muscle was injected with an equal volume of saline to serve as a control. After one week, the animals were euthanized, and both superior rectus muscles were removed and assayed physiologically using an in vitro apparatus. Muscles were stimulated at 1, 10, 20, 40, 100, 150 and 200 Hz to determine differences of both twitch and tetanic force production. Treatment and control superior rectus muscles from a separate group of animals were examined histologically. Results: One week after a single injection of IGF–I, low–frequency stimulation of treated muscles yielded a small increase in force generation compared to contralateral control muscles. At stimulation frequencies of 40 Hz and above, however, force generation was significantly elevated in the IGF–I–treated superior rectus muscles. Generated tension was 11% over control at 40 Hz, increasing to 18% over control at 200 Hz. These changes reflect a 29% increase in eom cross–sectional area in the global layer of treated muscles when compared with control. Conclusions: A single injection of IGF–I results in a modest increase in force generation at higher stimulation frequencies. Previous work in our laboratory demonstrated that IGF–II had a more pronounced effect at all the stimulation intensities (+45% over control at 200 Hz). Together, however, these studies demonstrate the potential utility of injectable growth factors for increasing eom strength. On–going drug–delivery studies will hopefully elucidate means of extending treatment effect to make such agents clinically useful.
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