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L. K. McLoon, B. C. Anderson, S. P. Christiansen; Long-Term Application of Bone Morphogenetic Protein-4 Results in Significant Decreases in Muscle Force Generation in Rabbit Extraocular Muscle. Invest. Ophthalmol. Vis. Sci. 2010;51(13):5823.
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© ARVO (1962-2015); The Authors (2016-present)
Potential options for pharmacological treatment of strabismus are expanding with the development of new agents that increase or decrease muscle force generation. Our earlier work showed that bone morphogenetic protein-4 (BMP-4) has the potential to reduce extraocular muscle (EOM) force 1 week after a single injection. In this study, the effect of sustained-release BMP-4 on EOM force was assessed after one, three and six months.
Sustained-release pellets were prepared which released 1microgram per day of BMP-4 over a period of 3 months. In anesthetized adult rabbits, a BMP-4 pellet was placed deep to the superior rectus muscle. The contralateral side received a placebo pellet as a control, randomizing the treated orbit. Six animals per time point were implanted. After 1, 3 and 6 months, the animals were euthanized, and the superior rectus muscles from both sides were removed and assayed physiologically. Muscles were stimulated at increasing frequencies to determine force generation.
After one and three months, muscle force per gram as well as force per cross-sectional areas were significantly decreased compared to the contralateral controls. By one month, force generation was decreased by 25-30%. By three months, force generation was decreased by 30-50%, depending on stimulation frequency. In contrast to other agents examined previously, force generation was still significantly decreased at 6 months, 3 months after BMP-4 elution ended.
Previous approaches to weakening the extraocular muscles for strabismus treatment used toxins or immunotoxins. The decreased force generation caused by BMP-4 suggests that it is possible to use a more biological approach to decrease muscle strength in vivo by means of myogenic signaling factors. Titratable, naturally occurring myogenic signaling and growth factors in antagonist-agonist pairs of extraocular muscles may provide safe, efficacious, non-surgical treatment options for patients with strabismus.
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