Abstract
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