New Retinal Cell Discovery Paves Way for Sight-Restoring Transplants

A new understanding of retinal cell development may help pave the way for future retina transplants, which could restore sight to people whose conditions currently have no effective treatments, according to researchers at the Perelman School of Medicine at the University of Pennsylvania. Their findings were published today in Frontiers in Cell and Developmental Biology.

Currently, the transplantation of healthy photoreceptor cells-neurons that detect light in the retina at the back of the eye-is largely ineffective because very few of the donated cells successfully connect to restore vision. However, the treatment remains promising if an ideal cell population that is more likely to form connections could be found.

By identifying three different developmental stages of photoreceptor cells in mice-which the study group believes may have analogous cell populations in humans-the researchers hope to determine which cell population is most capable of forming neuronal connections in the eye. Their findings may help researchers identify which cells are most likely to survive transplantation and integrate into the eye, leading to improved treatment outcomes.

We plan to isolate and transplant each subgroup individually, in the hopes that transplanting a more pure cell population will improve future cell-based therapies to improve vision in late-stage blinding conditions."

Katherine Uyhazi, Assistant Professor of Ophthalmology, University of Pennsylvania 

Differences in Cells and the Possibilities They Contain

Retinal diseases are a leading cause of blindness, affecting millions of people worldwide. Many of these conditions are inherited, while others, such as age-related macular degeneration, do not have a known genetic cause. Current treatments are aimed at slowing or stopping vision loss, but cell-based therapies have the potential to reverse vision loss by replacing lost or damaged cells.

"We know that retinal development does not occur uniformly, but in waves," Uyhazi said. "There is a mix of developmental cell stages present at any given chronological age during retinal development." Learning more about retinal development presented an opportunity to optimize retinal regeneration in disease.

Which is Which

By using single cell RNA sequencing, which can analyze how genes are expressed in individual cells, first author Joseph Yano, a PhD candidate in Uyhazi's lab, was able to identify three distinct states of developing photoreceptor cells: early, mid, and late. 

The team further showed that there may be comparable populations of cells in human retinal organoids, which are three-dimensional lab-grown structures that mimic structures in the human eye.

What's Happening Now

Following up on their discoveries, Uyhazi and her team are now working on methods for isolating and transplanting each of these cell states in the retina. Early cells are more similar to stem cells and may better survive transplantation, while late cells are more similar to retinal cells that can respond to light.

Through these further experiments in mice, the team hopes to identify a "goldilocks" stage of cell that is best suited to help repair the retina.

This work was supported by grants from the National Institutes of Health (T32 HD083185, K08EY031754, R01EY036824), the National Cancer Institute (P30 016520), and the Foundation Fighting Blindness (CD-CL-0823-0868-UPA).