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Glaucoma-linked gene may help insulate optic nerve

August 12, 2013

Researchers are making progress toward understanding how some cases of glaucoma begin. A new study from the National Eye Institute reveals that myocilin—a protein linked to a significant fraction of glaucoma—is needed to insulate peripheral nerves. The researchers theorize that myocilin could perform a similar function in the eye.

Glaucoma is a group of disorders that damage the optic nerve, which is the connection between the eyes and the brain. An increase in eye pressure is a major risk factor for the disorder. Genes also play a role. Mutations in the myocilin gene have been found in up to four percent of people with adult-onset glaucoma and 10 percent with juvenile-onset glaucoma.

Researchers have long believed that myocilin helps maintain normal eye pressure. It’s found at high levels within a sponge-like drainage system that regulates pressure inside the eye. But mice lacking the myocilin gene seem to have a normal drainage system, raising the possibility that the gene might be needed elsewhere.

In the new study, NEI researchers explored the role of myocilin in other tissues in these mice, focusing on a peripheral nerve that connects the spinal cord to muscles in the leg. The study was led by Stanislav Tomarev, Ph.D., who heads the NEI Section on Retinal Ganglion Cell Biology.

“We were surprised to see that myocilin has essential functions in the peripheral nerves,” Dr. Tomarev said.

He and his team published their results in the Journal of Biological Chemistry. They found that myocilin appears to promote the formation of myelin—the insulation that protects nerve fibers and enables them to rapidly transmit electrical signals. Mice lacking myocilin had thinner myelin in their peripheral nerves. Several structural proteins that are normally found within myelin were also missing or reduced. Thanks to these data, the researchers are now examining whether myocilin plays a similar role in the optic nerve. They reason that an abnormal myelin sheath could make the optic nerve susceptible to damage, leading to glaucoma.

Until now, there was little reason to suspect this new role for myocilin, since mutations in the myocilin gene do not appear to cause peripheral nerve disorders. A related protein called gliomedin may explain why, Dr. Tomarev said. Gliomedin is mostly absent from the eye, but is present in peripheral nerves, where it could compensate for the loss of myocilin, he said.

Reference: Kwon HS, Johnson TV, Joe MK, Abu-Asab M, Zhang J, Chan CC, Tomarev SI. “Myocilin Mediates Myelination in the Peripheral Nervous System through ErbB2/3 Signaling.” Journal of Biological Chemistry, July 2013. DOI: 10.1074/jbc.M112.446138.