It’s just been announced that Jeffrey Goldberg, MD, PhD, of the University of California, San Diego (UCSD) will share a $1 million grant from the U.S. Department of Defense (DoD) for a two-year project to develop whole-eye transplantation techniques in an animal model.
Goldberg is professor of ophthalmology and director of research at UCSD’s Shiley Eye Center and a 2010-12 BrightFocus grantee. The DoD project hinges off his BrightFocus-supported research, completed while Goldberg was at University of Miami, where he investigated cell therapy techniques to enhance optic nerve regeneration in a model of axon injury that mimics glaucoma.
Goldberg is currently collaborating on a 2013-15 BrightFocus grant to Kenneth J. Muller, PhD, at University of Miami, who’s investigating ways to transplant retinal ganglion cells (RGCs) into retinas in a mouse model of glaucoma.
While the prospect of eye transplants in humans is years and possibly decades off, that is indeed the “prize” that DoD has its eye on by awarding the two-year grant. It will be shared among three institutions: Goldberg and his team at UCSD, along with researchers at University of Pittsburgh Medical Center and Boston Children’s Hospital/Harvard University.
U.S. military personnel sustained an estimated 186,855 eye injuries, mostly related to traumatic brain injury, during the wars in Iraq and Afghanistan from 2000-10. There’s hope that in some of those individuals, vision might be restored.
The potential of eye transplants, if realized, would also benefit individuals who lost their vision due to other structural or functional problems in the eye, including the estimated 120,000 Americans who are legally blind due to optic nerve damage caused by glaucoma.
“We talk about repairing the nerve in glaucoma or AMD, but this research is allowing scientists to think much more broadly to a future where whole eye transplants are not so far away,” commented BrightFocus VP of Scientific Affairs Guy Eakin, PhD.
“Certainly Jeff’s earlier BrightFocus grant will inform the science behind this surgery, as will other regenerative therapies we’ve supported,” Eakin said.
“Rewiring” the Eye Is a Huge Challenge
The goal of the DoD project, over two years, is to transplant a whole eye in an animal model and successfully demonstrate neuronal regrowth from the donor’s eye to the recipient’s optic nerve.
“A whole eye transplant could be a holy grail for vision restoration,” Goldberg said in a UCSD news release, adding: “It is in the realm of scientific plausibility.”
The greatest challenge—and the one Goldberg, Muller, and others have been working on—lies in “rewiring” the RGCs into the optic nerve in order to recover an electrical response to light and, ultimately, recreating the eye-brain connection to restore vision.
The optic nerve is a bundle of more than one million nerve fibers, or axons, which carry visual information from the eye to the brain. When damaged by glaucoma, macular degeneration, and other blinding diseases, optic nerve axons, unlike most tissues in the body, are not programmed to regenerate. Vision loss is permanent.
To achieve the goal of eye transplantation, “the biggest scientific hurdle is not hooking up all the eye’s tiny blood vessels or its musculature,” Goldberg said. “It's that when you cut the optic nerve, the nerve cells do not regrow.”
Previous experiments at University of Pittsburg Medical Center were successful at transplanting whole eyes in rats that had been genetically bred to minimize tissue rejection. However, even though retinal tissue in the transplanted eyes appeared healthy, the optic nerves did not recover and regenerate connections.
Thus, the main focus of the research will be on ways to “trick” the optic nerve into regenerating and reconnecting the eye's neuronal wiring. Separately, the grantees have been trying to rebuild that eye-brain connection using cell therapy and other techniques that enhance signaling and encourage growth of neurotrophic factors (i.e., proteins that are involved in growth, survival and maintenance of developing neurons). Now they’ll explore whether the molecular techniques they’ve worked on separately can be combined for greater effect.
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