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9.20.2016

Research Team Awarded $2 Million by NIH to Study Targets to Promote Axon Regeneration

A team of University of Miami Miller School of Medicine investigators has been awarded a three-year $2 million grant from the National Institutes of Health to study biological treatments for blindness — specifically factors that affect neural regeneration in the retina.

The Miller School team was one of only six nationwide to receive funding as part of the National Eye Institute Audacious Goals Initiative (AGI) — a targeted effort to restore vision by regenerating neurons and their connections in the eye and visual system.

Two neuroscientists from The Miami Project to Cure Paralysis and the Department of Neurological Surgery — Kevin Park, Ph.D., associate professor, and Vance Lemmon, Ph.D., the Walter G. Ross Distinguished Chair in Developmental Neuroscience and professor — will partner with Sanjoy Bhattacharya, Ph.D., professor of ophthalmology, to direct the grant-winning research project, titled “Novel Targets to Promote RGC Axon Regeneration: Insights from Unique Retinal Ganglion Cell Cohorts.”

Park and Lemmon will use RNA sequencing in mouse retinal ganglion cells to identify differences in the expression of genes in regenerative versus non-regenerative retinal ganglion cells. In parallel, Park and Bhattacharya, of Bascom Palmer Eye Institute, will use mass spectrometry to determine what lipids (or fat molecules) may give subclasses of retinal ganglion cells more robust regenerative capacities. The researchers will then perform a set of experiments aimed at understanding the function of the genes found to be involved in regeneration. The most promising gene candidates will be used as a therapy aimed at regenerating the optic nerve in a mouse model with optic nerve injury.

“Some central nervous system neurons can regenerate their axons, while others cannot,” said Park. “We know very little about the mechanisms that give rise to such a difference in regeneration capacity. If one can identify what allows regeneration in these unique neurons, we could potentially promote strong regeneration in neurons in general.”

Most irreversible blindness results from the loss of neurons in the retina, which is the light-sensitive tissue in the back of the eye. Many common eye diseases, including age-related macular degeneration, glaucoma and diabetic retinopathy, put these cells at risk. Once these neurons are gone, humans have little if any capacity to replace them. The study will look at central nervous system cells and, if successful, could provide applications for other neurodegenerative diseases, disorders and injuries like spinal cord and brain injuries.

“Understanding factors that mediate the regeneration of neurons and the growth of axons is crucial for the development of breakthrough therapies for blinding diseases,” said National Eye Institute (NEI) Director Paul A. Sieving, M.D., Ph.D. “What we learn through these projects will have a health impact beyond vision.”

NIH hopes the six funded projects will add to the knowledge base from several recent key advances. Researchers recently reported a technique that increases the regenerative capacity of retinal axons in a mouse model of optic nerve injury, a model commonly used to study glaucoma and other optic neuropathies. Progress also has been made in identifying factors that either stimulate or inhibit regeneration of neurons required for vision. The newly funded projects will further this area of research by identifying cues that guide axons to appropriate targets in the brain, allowing functional connections to re-establish between the eye and the visual processing system.

For more information about these and other AGI projects, visit the NEI AGI webpage at www.nei.nih.gov/audacious.

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