Abstract
Purpose: :
Strabismus is a misalignment of the visual axis that can be due to a weak extraocular muscle. We have previously shown that insulin-like growth factor-1 (IGF1) and cardiotrophin-1 (CT1) increase extraocular muscle strength, mass, and fiber diameter in embryonic chickens (Chen and von Bartheld, 2004, IOVS 45:3538-3545). Here, we determined whether these trophic factors have effects on juvenile extraocular muscles. This information is relevant for assessing the potential role of these factors in pharmacological treatment of strabismus in children.
Methods: :
Following two injections, 3 days apart, of IGF1 and/or CT1 in the orbit with different dosages (0.5µg or 5µg), we quantified several parameters of chicken superior oblique extraocular muscle at 2 weeks of age, including contractile force in situ (twitch and tetanic tension, Croes and von Bartheld, 2007, J Neurosci Methods 166:53-56), myofiber number and diameter, and muscle mass, and compared with sham-injected controls (n=6-9 per group).
Results: :
Treatment with IGF1 (0.5µg or 5µg) significantly increased single-twitch force generation by 18.8% and tetanic tension by 15.7%, with no additional increase with the higher dose. Injection of CT1 (5µg, but not 0.5µg) significantly increased twitch tension by 25.3% and tetanic tension by 18.1%. The two combination treatments (IGF1/ 0.5µg with CT1/ 0.5µg, IGF1/ 0.5µg with CT1/ 5µg) had similar effects on increasing muscle strength (twitch tension 18.4%-23.6% and tetanic tension 18.5%-18.7%) and muscle mass (17.3%-20.5%). The single-drug treatments increased the mean of the muscle mass (by 9%-10%), but without statistical significance, except for CT1 (5µg) treatment (22.3%). The total number of myofibers was not increased. The overall myofiber diameter was not altered, indicating that increased strength may be due to increased myofiber length rather than diameter.
Conclusions: :
Exogenous IGF1 and CT1 increase the extraocular muscle strength and mass with different potencies. IGF1 is effective already at lower concentration (0.5µg) than CT1. The effects of IGF1 and CT1 are not additive and therefore may work by the same mechanism. The mechanism of increasing muscle strength appears to involve increased length rather than hypertrophy of myofibers. Morphological studies at the ultrastructural level currently examine whether particular myofiber types may respond to these trophic factors. Our data provides new information that is relevant for the development of growth-factor based strategies to treat strabismus in children.
Keywords: strabismus: treatment • extraocular muscles: development • growth factors/growth factor receptors