Stem Cell-Derived Retinal Transplants May Improve Vision in Mice with End-Stage Retinal Degeneration
New research shows that stem cell–derived transplants may help restore vision in end-stage retinal degeneration.
A research group in Japan has shown that retinal transplants derived from stem cells can restore some vision in a mouse model of end-stage retinal degeneration. The investigators demonstrated that the grafts integrated with the host tissue, restored some light response in mice with the transplants, and could transmit light signals to the host’s neural cells.
“Our data provide a proof of concept for transplanting ESC/iPSC [embryonic stem cell/induced pluripotent stem cell] retinas to restore vision in end-stage retinal degeneration,” write the authors. The results were published in Stem Cell Reports.
The researchers used mice with no retinal outer nuclear layer (part of the photoreceptor layer of rods and cones) because this model is relevant to clinical practice. Cell-based treatment would most likely be used in patients with end-stage retinal degeneration and no functioning outer nuclear layer, they write. Their previous experiments showed that stem cell—derived retinal tissue could develop into an outer nuclear layer. Other studies indicated that transplants of photoreceptor cells alone (not sheets of retinal tissue) possibly restored a light response in mice with no outer nuclear layer, but these cells did not fully integrate with the host tissue and did not last long. The investigators’ aim with this study was to evaluate the visual function of the outer nuclear layer grafts.
The researchers first used gene labeling to verify that the retinal grafts integrated with the host tissue. “Our observations revealed that host bipolar cells extend their dendrites into the graft, sometimes even through the remaining graft inner cells,” they write.
In a test of visual function, some of the mice with retinal grafts were able to respond to light signals, regardless of whether grafts were placed in one or both eyes. Because of the difficulty in proving visual function in mice, the researchers devised a learned-response avoidance test. They trained mice with light and/or sound signals to avoid a noxious stimulus. When both light and sound signals were given, mice with retinal degeneration performed as well as those with normal retinas. When only the visual signal was given, only the mice with normal retinas learned to avoid the stimulus. After retinal transplantation, however, 4 of 10 mice with transplants in both eyes and 5 of 11 mice with transplants in one eye responded to light signals.
The researchers treated all transplanted mice with 9-cis retinol acetate, which improves vision in mice with dysfunctional retinal pigment epithelium. Although they did not test transplanted mice without this treatment, they report that 9-cis retinol acetate had no effect on light responses in mice without retinal transplants and therefore was not likely to have altered the results in mice with transplants.
The final functional test, ex vivo microelectroretinography and retinal ganglion cell recordings, showed that light signals were transmitted from the grafts to the host’s neural cells. “After transplantation, marked light-responsive mERGs [microelectroretinograms] were recorded in the grafted area in all the samples tested,” write the authors. However, amplitudes were smaller in grafted tissue than in normal retinas.
The results show that stem cell—derived retinal tissue can develop into a mature outer nuclear layer and respond to light in a mouse model of end-stage retinal degeneration, conclude the authors. They report that they are currently testing a similar graft derived from human stem cells.
Dr. Laurie Anne Walden received her doctorate in veterinary medicine from North Carolina State University. After an internship in small animal medicine and surgery at Auburn University, she returned to North Carolina, where she has been in small animal primary care practice for over 20 years. Dr. Walden is also a board-certified editor in the life sciences and owner of Walden Medical Writing, LLC. She works as a full-time freelance medical writer and editor and continues to see patients a few days each month.