Facial Muscles Offer Insight into Duchenne Muscular Dystrophy

Researchers explore why ocular and facial muscles are spared in patients with Duchenne muscular dystrophy.

Biochemical and physiological characteristics of a group of muscles that control the eyelids called orbicularis oculi were examined during a recent study on Duchenne muscular dystrophy.

The study, published in The Journal of General Physiology, used healthy human muscle cell cultures and differentiated human myotubes grown on glass coverslips.

Researchers examined the excitation-contraction coupling (ECC) process and calcium homeostasis in the orbicularis oculi, extraocular muscles, and the quadriceps.

The ECC process uses an electrical signal that is converted into a chemical signal, causing a muscle contraction. The results of the study found that ECC machinery and calcium regulation of human orbicularis oculi were found to be more similar to quadriceps than the extraocular muscles.

“Although gene expression in orbicularis oculi is quite different from that in quadriceps, the expression of proteins involved in the ECC process is similar in both cell types," the study authors wrote.

During the study, high levels of dystrophin were found in the quadriceps, in addition to low levels of utrophin. However, the levels for dystrophin were low in the orbicularis oculi and extraocular muscles, plus utrophin levels were high.

“Our results concerning the expression of utrophin are interesting and most likely explain why ocular and facial muscles are spared in patients with Duchenne muscular dystrophy,” the authors wrote.

Researchers also found that dystrophin and utrophin might share distinct binding partners due to differing subcellular distribution, or at least in myotubes.

Dystrophin distribution consists of a punctate membrane, while utrophin has a patchy, filamentous distribution concentrated within certain subcellular domains.

Additionally, dystrophin-deficient mdx mouse studies showed promise in utrophin being able to functionally compensate in vivo for the lack of dystrophin.

“This supports current strategies aimed at modulating utrophin expression in the therapy for Duchenne muscular dystrophy,” the authors wrote. “Taken together, these studies show that satellite cells derived from different muscles are primed and will follow the developmental characteristics of their muscle of origin, a property that can be exploited in laboratories devoted to tissue engineering.”