The Characterization of the Neuromuscular Junction in Patients with Strabismus: A Preliminary Study

Past Event Date: 

Speaker: 

Jolene Rudell, Clinical Fellow in pediatric ophthalmology at University of Washington and Seattle Children’s Hospital

Host: 

William Good

Meeting room: 

Room 204 - Main Conference Room

Event Type: 

Abstract:

Strabismus is a common cause of visual morbidity in children in the United States. There are known factors associated with strabismus, such as refractive error or monocular status with poor vision in one eye. However, the specific mechanisms of how ocular misalignment manifests is still unknown. There is some evidence in literature that central processes and a disruption in neuronal pathways play a role in strabismus. Peripheral factors such as the health of the extraocular muscle and neuromuscular junction development have not been well studied, and its contribution to the cause of strabismus is thought to be important but essentially unknown. This is the first study to examine the morphology of the neuromuscular junction at extraocular muscles in patients with strabismus. We hypothesize that the neuromuscular junction morphology is abnormal in these patients. Muscle samples were obtained from patients with strabismus during surgical resections, and fresh frozen and sectioned. The neuromuscular junction was identified with immunostaining with synaptic markers, and then analyzed with fluorescent microscopy. Preliminary data suggests the morphology of the neuromuscular junctions in patients with strabismus is abnormal compared to what is known about normal human extraocular muscle. In addition, one of our muscle samples had substantially fewer synapses compared to the others, which suggests that the extraocular muscle may be more abnormal in certain types of strabismus over other types. Overall, this is the first study to examine the morphology of the neuromuscular junctions in patients with strabismus. Additional studies will need to be done to look at age matched controls in patients without strabismus, as very little is even known about the morphology of neuromuscular junctions in normal human extraocular muscle. This study suggests that neuromuscular junction morphology is likely important for the development of strabismus, and knowing more about the role of the peripheral muscle in strabismus patients and the basic mechanisms of strabismus has significant potential to impact treatment, management, and possibly even prevention of ocular misalignment in these patients.

We examined extraocular muscle samples from patients with strabismus during surgical resections and immunostained them with synaptic markers 

Prior studies have identified two types of synapses that are present in normal human extraocular muscles, the “en plaque” synapses that are localized to fast twitch muscle fibers, and the “en grappe” synapses that are localized to slow twitch muscle fibers. Synaptic immunomarkers were used to identify the morphology of the neuromuscular junctions in strabismus patients by taking muscle samples during surgical resections. These samples were then analyzed with fluorescent microscopy. Preliminary results show that in patients with strabismus, there appears to be an abnormal ratio of the two types of synapses previously described in normal human extraocular muscle, the “en grappe” and the “en plaque” synapses. Also, in one of our samples, a substantial fewer number of synapses were found in this muscle sample compared to the others, which suggests that the peripheral muscle may be more abnormal in certain types of strabismus over other types of strabismus. Overall, this is the first study to examine the morphology of the neuromuscular junctions in patients with strabismus. Additional studies will need to be done to look at age-matched controls in patients without strabismus, as very little is even known about the morphology of neuromuscular junctions in normal human extraocular muscle. This study suggests that neuromuscular junction morphology is likely important for the development of strabismus, and knowing more about the basic mechanisms of strabismus has significant potential to impact treatment, management, and possibly even prevention of ocular misalignment in these patients.