Restoring Vision Through Fetal Retinal Cell Transplants
In animal trials, researchers at the University of California, Irvine, have restored normal neural activity in the visions centers of the brain after fetal retinal cell transplants.
by Todd Farley
Could eye diseases like age-related macular degeneration and retinitis pigmentosa not just be treated but cured? Based on their exciting animal study released in December of 2018, “Detailed visual cortical responses generated by retinal sheet transplants in rats with severe retinal degeneration,”¹ researchers at the University of California, Irvine (UCI), believe so.
“We need funding to continue this research, and there are many more steps to go,” says David Lyons, PhD, associate professor of anatomy and neurobiology and director of graduate studies at the UCI School of Medicine as well as lead author of the study. “But it seems like that could be doable.”
Dr. Lyons’ lab normally studies how neurons in the brain respond to visual stimuli — how those “computations in the brain are made.” For this study, Dr. Lyons collaborated with another lab on the UCI campus to see how transplanting healthy cells into the eyes of rats with degenerated retinas might affect their vision. While Lyons characterized the work as initially being more of a “side project,” its positive results turned it into something “really interesting” for all involved.
Rat Model of Retinal Degeneration
“We used a rat model of retinal degeneration,” Dr. Lyons explains. “Those rats had a transplant of healthy retinal tissue to replace the degenerated retina. What we showed was that deeper in the brain, in the target regions of the retina, neurons in the rats with transplanted retinal tissue responded indistinguishably from those of normal rats. In other words, the transplanted retinal tissue ended up providing quality input that the brain interpreted as being as good as the normal input.”
The rats in the study originally had been able to see but lost their vision due to retinal degeneration. Sheets of fetal retinal cells were harvested from unborn healthy rats and then, under sterile surgical conditions, transplanted into the rats with retinal degeneration. Using a special tool, the transplanted sheets of retinal cells were placed over approximately 20% of the degenerated retinas. Limiting the size of the transplant to 20% of the retina allowed the remaining 80% of the retina to serve as the experimental control.
Positive Results
While they were not universally integrated into the degenerated retinas, those transplanted cells provided positive results. Along with producing neural activity in the blind rats that could be characterized 3 months after the procedure as almost “normal,” Dr. Lyons was also able to see that the transplanted retinas maintained strong connectivity to the brain. (Vision was tested after 3 months because other studies indicate that it takes 3 months for retinal cells to integrate themselves into that part of the eye). That connectivity is important: the initial visual image detected by the retina is then relayed deeper into the part of the brain, where higher-level visual processing takes place.
“Our study is saying the end result is a ‘seeing rat,’ but this is based on the function of their brain, not necessarily behavioral vision tests,” Dr. Lyons explains. “While it’s a little early to say what the scope of the rat’s vision is, the major brain regions involved in vision indicate that their vision is performing very well.”
Study Limitations
The researchers were able to differentiate between the donated and native retinal cells by a biomarker in the form of a a fluorescent stain. The biomarker also allowed them to identify at least one concern regarding the work.
“There are some shortcomings to the study,” Dr. Lyons concedes. “One issue that we mentioned in the paper is that really only half of the neurons responded. So, even though half responded very well, half the neurons didn’t respond at all, which is a big difference between a normal rat and these recovered rats.”
Dr. Lyons isn’t exactly sure why some of the neurons responded to the transplant process and others didn’t. He surmises that it just could that when the original retina degenerated, some of the neurons (because of a lack of any “input” at that point) simply lost their ability to function. In any case he recognizes that this question still needs to be answered.
“That’s something else to be figured out,” he says. “We’re trying to develop therapies that will help the retina integrate better into the animal, basically like having practice exercises to help form the synapses, but until all the neurons are getting the input, our work is essentially incomplete.”
Retinal sheet transplants have previously been performed in both animals and humans, but in both cases results were mostly rudimentary, demonstrating only the ability of these transplanted retinas to detect light. The UCI study, on the other hand, demonstrates not just that the rats with transplanted cells can detect light but also that they can became sensitive to a number of different visual stimuli, including size, orientation, and contrast.
Looking Forward
While this UCI study shows promise, Dr. Lyons recognizes that there is more work to do. Next it needs to be determined if the “higher regions of the visual cortex” are also functioning appropriately after the transplant. In addition, the responsiveness of the brain needs to be improved so that more than just half the transplanted neurons are reacting normally — something Dr. Lyons hopes can be done through different types of retinal stimulation practices.
Equally importantly, behavioral tests need to be done with the recovered rats to ensure that they can actually see, not just that they have encouraging signs of neural activity in the brain. For all the questions that remain, however, Dr. Lyons is excited about what he has so far seen.
“The ultimate goal of this work is that these retinal transplants might one day be used on people with retinal degeneration,” he says. “And the results of this study do show the great potential of retinal transplants one day being able to restore vision in people who have lost theirs due to certain diseases.”
Reference:
- Foik AT, Lean GA, Scholl LR, et al. Detailed visual cortical responses generated by retinal sheet transplants in rats with severe retinal degeneration. J Neurosci. 2018;38(50):10709-24. https://www.ncbi.nlm.nih.gov/pubmed/30396913
