Looking through the lens of his confocal microscope, Per-Olof Berggren peers at the colonies of beta cells that he injected just in front of the mouse's iris. He watches its dark eyes light up with different fluorescent labels that mark the physiological processes of the transplanted beta islet cells. It's a procedure he hopes could one day be used in humans to treat diabetes. But for now, Berggren is focused on the basic science of the technique he designed. "If you can use the eye to look out," says Berggren, "why not use the eye as a body window to look in?"
Berggren's group at Stockholm's Karolinska Institute, including colleague Stephan Speier, worked with the Diabetes Research Institute in Miami to harvest, from transgenic mice, beta islet cells that expressed green fluorescent protein when producing insulin. They injected beta islets into the pocket between the iris and cornea and then watched for the growth of blood vessels labeled with a red fluorescent stain - one indication of healthy engraftment (Nat Med, 14:574-8, 2008).
"I think this is very important for islet transplant research; we are missing a good model," says Juan Contreras, director of the Southern Tissue Center at the University of Alabama School of Medicine, who was not involved in the research. The model allows researchers to see the physiology of the cells responsible for producing insulin and maintaining normal blood sugar, in real time without sacrificing the animal. The eye is a somewhat immunoprivileged site, which protects transplanted cells from the immune attack they would experience in other parts of the body. "This is honestly the first time that we can see what is happening with the islet graft," says Contreras.
Islet cells are increasingly being transplanted along the liver of diabetic patients to try to restore insulin production. However, over time, in some patients the transplanted islets cells stop producing insulin. Researchers still aren't sure why, but the extent to which blood vessels grow into the newly transplanted beta cells may play a role. "This is a powerful technology to look at the islet graft vascularization, which is becoming a major problem in transplantation," says Contreras. The "thrilling" part, adds Berggren: When he injected beta islet cells into the eyes of diabetic mice, the cells produced enough insulin to regulate blood glucose to normal levels.
The first obvious question is whether such transplantations could impair vision. Berggren says he didn't see any major changes in mouse behavior that might suggest irritation in the eyes, or impaired vision, "but we haven't done a real eye test." The other question is whether it would be possible to pack enough beta cells into the human eye to eliminate diabetes. Humans require more beta cells than mice, and the area between the iris and cornea is much smaller and flatter in humans than in mice. "You have two to four millimeters of (beta cell) tissue," which must fit into "less than one millimeter of space," says Camillo Ricordi, a surgeon at the Diabetes Research Institute, and a coauthor on Berggren's paper. He adds that it might be possible to implant more cells beneath the iris, out of the way of the lens. And when the researchers took their results to ophthalmologists at The University of Miami's Bascom Palmer Eye Institute, "there was a surprising degree of enthusiasm," says Ricordi. "From a technical, surgical, and immunological perspective," says Victor Perez, an ophthamologist and ocular immunologist at Bascom, "I think this is really doable."
But time will tell. "There are a lot of issues" associated with using this technique in humans, says Berggren. "I didn't think it would be possible."