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Christy Willoughby, Linda K McLoon, Michael J Mustari; Oculomotor System Plasticity After Sustained Unilateral Brain-Derived Neurotrophic Factor Treatment of the Extraocular Muscles: A Novel Treatment for Strabismus. Invest. Ophthalmol. Vis. Sci. 2014;55(13):2570.
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Conjugate gaze and stereopsis are established and fine-tuned in early life by visual experience. Strabismus is an oculomotor disorder where eye position is misaligned. If left untreated, strabismus persists through adulthood and is the leading cause in the United States of amblyopia. A common strabismus treatment, surgery, has high failure rates, possibly because strabismus only alters the highly adaptable extraocular muscle. Neurotrophic factors present a potential alternative treatment approach because of their actions both on muscle and motor neurons that direct eye position and movement. We assessed if unilateral sustained delivery of brain-derived neurotrophic factor (BDNF) to an extraocular muscle could alter the eye position of infant non-human primates.
Sustained-release pellets of BDNF were implanted unilaterally on the lateral rectus muscle of two normal infant non-human primates. After three months of treatment, eye position was assessed with corneal light reflex testing. Extraocular muscle specimens were collected for histological analysis of changes in muscle morphology and innervation density from BDNF treatment. Muscle specimens were compared to two control infant non-human primates.
Unilateral sustained release of BDNF for three months to the lateral rectus muscle in infant non-human primates resulted in strabismus for both treated infant monkeys. Analysis of muscle specimens showed that neuromuscular junction density substantially increased in the treated extraocular muscle, suggesting that BDNF altered eye alignment by increasing motor neuronal control over extraocular muscle.
Our results demonstrate that unilateral sustained neurotrophic factor treatment in infant monkeys alters normal eye position. Our results suggest that altered signaling in the extraocular muscles can perturb the development of normal eye alignment, and may provide insight into causes of childhood strabismus. Our results also strongly support BDNF as a promising novel candidate treatment for strabismus. Future work will treat non-human primates with strabismus to determine the dosage of BDNF and duration necessary to improve/restore normal eye alignment.
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