"How the optic nerve develops and why it fails to regenerate after traumatic injury to the eye are very poorly understood," says Associate Professor David Sretavan, MD, PhD, explaining his groundbreaking investigations of optic nerve development.

"We have recently discovered that some of the molecules that help guide retinal nerve fibers (also known as axons) during development re-appear after injury to the optic nerve," he says. Dr. Sretavan's laboratory has identified three important molecules that are essential to optic nerve development: Netrin-1, EphB and Semaphorin-5A.

If these axon guidance molecules are shown to foster nerve regeneration, the findings may have implications for better treatment of optic nerve injuries and other conditions involving damage to optic nerve fibers including glaucoma.

Dr. David Sretavan's studies could lead to new treatment for optic nerve injuries and glaucoma damage.

Molecules Guide Nervous System Development

"In the past several years, our laboratory group has played a

very active role in elucidating the molecular mechanisms of optic nerve development," Dr. Sretavan says.

Dr. Sretavan's laboratory studies have focused on two major aspects of retinal axon growth and development. One, the molecular interactions that mediate axon outgrowth in the embryonic brain environment. Two, the guidance molecules that are re-expressed in the adult optic nerve following traumatic injuries.

Leveraging Research Findings

"We are attempting to leverage what we've learned from basic research on development of the visual system to dissect out the mechanisms at work in the adult optic nerve after injury and disease," Dr. Sretavan explains.

Behind this work are the techniques of cell and molecular biology, used to examine the genes and coded proteins. With in situ hybridization, researchers apply molecular probes to tissue, to detect specific genes. In cell culture studies, retinal tissue is maintained in a living state, and investigators test cell function in a culture dish. Investigators also use time-lapse microscopy of living cells and axons to examine living axons navigating within the optic nerve.

Glaucoma Studies

"An emerging view in glaucoma research is that the final common pathway leading to the loss of vision is pathological changes to the optic nerves," says Dr. Sretavan. "We are now embarking upon studies to determine whether the molecular changes associated with traumatic optic nerve injury are also induced by glaucoma."

Over the past eight years, Dr. Sretavan has carried out optic nerve studies with over a dozen highly trained post-doctoral fellows, students, and research technicians.

"We believe that studies of retinal axon guidance will further our understanding of visual system development," he says. " This research may also be important for future efforts to promote central nervous system re-generation or prevent axon loss, after disease or injury."