Miller School Researchers Transplant Retinal Ganglion Cells into Living Animals

A University of Miami Miller School of Medicine research team has successfully transplanted retinal ganglion cells into the eyes of living animals. The groundbreaking laboratory study also found that the new cells responded to light, a finding with potential clinical implications for glaucoma, macular degeneration and other retinal diseases.

“This is the first time transplanted retinal ganglion cells (RGCs) have survived and made integrated connections with existing retinal cells,” said Praseeda Venugopalan, Ph.D., a former neuroscience student at the Miller School who is now working at Genentech in San Francisco. “These findings present a promising approach to potential cell replacement strategies in conditions like glaucoma that lead to the loss of RGCs.”

Venugopalan was lead author of the study, “Transplanted Neurons Integrate into Adult Retinas and Respond to Light,” published recently in Nature Communications. Co-authors included Kenneth J. Muller, Ph.D., professor of physiology and biophysics, Miller School of Medicine, and Jeffrey Goldberg, M.D., Ph.D., former professor of ophthalmology at Bascom Palmer Eye Institute and now professor and chair of ophthalmology at Stanford University.

In the laboratory study, Venugopalan took RGCs that had been tagged with a genetic marker and injected them into the healthy eyes of 152 adult rats. Unlike prior studies using immature stem cells, the fully differentiated RGCs were able to form effective connections with the optic nerve to the brain in about one of six animals. “This is just a starting point,” she said. “More studies will be needed to see if RGCs make similar connections when transplanted into eyes with glaucoma or other diseases. Another question is whether automating the cellular transplantation process would produce more consistent results.”

Muller said one of the most exciting aspects of the study was demonstrating the functionality of the transplanted RGCs. “We recorded the electrical signals from the cells with the genetic markers, and found they responded to light, making shapes and patterns in the retina,” he said. “Now, we want to see how to improve the viability of the transplanted RGCs and increase the number of successful outcomes.”

Because neurons in mammals’ central nervous systems generally are not replaced, transplantation of replacement neurons to restore neural connections has become an important avenue for research for recovery from damage or disease. “There has been success in transplanting cells into the outer retina to replace degenerating photoreceptors as therapy for diseases like retinitis pigmentosa or age-related macular degeneration,” Muller said. “But the physiology of those photoreceptors is different than RGCs, which transmit information from the photoreceptors in the retina to the visual centers in the brain.”

The study was funded by BrightFocus Foundation, a non-profit organization supporting research into Alzheimer’s disease, glaucoma, and macular degeneration; the National Eye Institute; and Research to Prevent Blindness, Inc.

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