April 2010
Volume 51, Issue 13
ARVO Annual Meeting Abstract  |   April 2010
Long-Term Application of Bone Morphogenetic Protein-4 Results in Significant Decreases in Muscle Force Generation in Rabbit Extraocular Muscle
Author Affiliations & Notes
  • L. K. McLoon
    Ophthalmology, University of Minnesota, Minneapolis, Minnesota
  • B. C. Anderson
    Ophthalmology, University of Minnesota, Minneapolis, Minnesota
  • S. P. Christiansen
    Ophthalmology-Boston Med Ctr, Boston Univ School of Medicine, Boston, Massachusetts
Investigative Ophthalmology & Visual Science April 2010, Vol.51, 5823. doi:
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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)

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Purpose: : 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.

Methods: : 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.

Results: : 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.

Conclusions: : 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.

Keywords: strabismus: treatment • extraocular muscles: structure • strabismus 

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