Eye Muscles Resist ALS Progression, but More Research Needed to Understand Why

Patients with amyotrophic lateral sclerosis (ALS) have intact eye muscle movement, even at more advanced stages of the disease, according to new research. However, the reason remains unknown. Researchers say that discovering how this happens may help in the design of novel treatments to fight the loss of muscle activity in ALS patients.

The research results are part of a doctoral thesis conducted by Anton Tjust from Umeå University in Sweden.

Eye muscles are very different from other muscles in the body, primarily in the connections formed between their muscular cells and neurons (called neuromuscular junctions). ALS is known to destroy motor neurons in the brain and spinal cord, thereby affecting muscular activity, but this damaging effect seems to spare the eye muscles.

“We could see that the nerve connection to the eye muscles remains intact even in stages of the disease where a large proportion of neuromuscular junctions had been lost in leg muscles,” Tjust said in a news release.

“The loss of connection between nerves and muscles can be seen in rather early stages of the degenerative process,” he explained. “We can hence establish that eye muscle protection mechanisms are active at a relatively early stage of the disease. Our results do not, however, ascertain if the disease starts in the nerve connection or in [neurons].”

Previous studies carried out by Tjust’s team to address this question showed that certain types of muscle fibers present in the eye muscles are lost as ALS progresses. Up to one-third of one of these types, known as multiply-innervated muscle fibers, are lost in certain ALS patients.

“It seems like certain muscle fiber types in the eye muscles are not at all resilient to ALS. It is rather other fiber types in the eye muscles that preserve their functions so well,” Tjust said. “However, pinpointing these particular fiber types still remains to be done.”

Researchers then studied muscle stem cells present in the eye muscles to investigate whether these cells would retain muscle activity despite ALS progression. They found that the amount of muscle stem cells in the eye muscles of healthy individuals and ALS patients was not different.

This study also indicated that the amount of muscle stem cells in the arms and legs of ALS patients was normal or even increased, with different stages of cell activity and maturation, while in the eye muscles, the number of muscle stem cells was only moderate.

As similar results were found in healthy individuals, the team concluded that muscle stem cells are probably not affected by ALS progression and, as a result, cannot be the reason why muscles in the arms and legs stop working in patients, while eye muscle function remains intact.

“The fact that the eye muscles actually retain their function so well in ALS patients suggests that there nevertheless is some form of protective mechanism,” Tjust said. “… we as researchers have an obligation to continue conducting research until we have an efficient treatment to offer.”