Insulin-like Growth Factor-1 and Cardiotrophin 1 Increase Strength and Mass of Extraocular Muscle in Juvenile Chicken

Abstract

Insulin-like growth factor 1 (IGF1) and cardiotrophin 1 (CT1) are known to increase the strength of extraocular muscles in adult and embryonic animals, but no information is available for the early postnatal period, when strabismus treatment in humans is most urgent. Here the authors sought to determine whether these trophic factors strengthen juvenile maturing extraocular muscles and gain insight into mechanisms of force increase. After two injections of IGF1, CT1, or both with different dosages in posthatch chickens, the authors quantified five parameters of the superior oblique extraocular muscle at 2 weeks of age: contractile force, muscle mass, total myofiber area, myofiber diameter, and number of proliferating satellite cells labeled by bromodeoxyuridine. Treatment with IGF1, CT1, and combination of IGF1 and CT1 significantly increased contractile force by 14% to 22%. CT1 and combination treatment significantly increased muscle mass by 10% to 24%. IGF1/CT1 combination treatment did not have additive effects on strengthening muscles, compared with single-drug treatments. Myofiber area increased significantly with IGF1 and CT1 treatment in proximal, but not distal, parts of the muscle and this was due to increased fiber numbers or length (IGF1) or increased diameters of global layer myofibers (CT1). Trophic factors increased the number of proliferating (bromodeoxyuridine-labeled) satellite cells in proximal and middle segments of muscles. Exogenous IGF1 and CT1 strengthen extraocular muscles during maturation. They predominantly remodel the proximal segment of juvenile extraocular muscles. This information about muscle plasticity may aid the design of pharmacologic treatment of strabismus in children during the "critical period" of oculomotor maturation.