By David N. Leff
Editor's note: Science Scan is a roundup of recently published biotechnology-relevant research.
"Look in a mirror at your own eye," suggested neurobiologist Derek van der Kooy at the University of Toronto, "and focus on the iris, the round, colored part that's blue, green or brown in people. And if you look on the outside rim of the iris - the ciliary margin," he went on, "just before you get to the white part of your eye, you'll see a small number of dark pigmented cells.
"One in 500 of those cells are stem cells," van der Kooy pointed out. "And it turns out that the same region of the eye in frogs and in fish is a region that adds new photoreceptors throughout their adult life. We've shown that stem cells, or similar cells - although present in mammals, including humans - under normal conditions never add new cells to the eye.
"What happens," he explained, "is that very potent inhibitor controls prevent that cell from proliferating normally in adult humans and other mammals."
Van der Kooy is senior author of an article in Science dated March 17, 2000, titled: "Retinal stem cells in the adult mammalian eye."
"We knew that the business end of the eye," he told BioWorld Today, "grows photoreceptor cells and retinal epithelial cells out of the brain during embryological development. We wondered whether a stem cell might also be present in the adult eye, and looked in particular at one little region in the eye - that ciliary margin. The mature mammalian retina," van der Kooy pointed out, "is thought to lack regenerative capacity. In our paper, we report the identification of a stem cell in the adult mouse eye, which represents a possible substrate for retinal regeneration.
"And I guess why people are interested is that there are quite a lot of implications. If everyone has a stem cell present in his or her own eye, then a long-term solution for people who have eyesight problems would be to activate that stem cell to regenerate the cells that are missing in the eye, and hopefully restore their vision."
He continued: "As soon as we found an eye stem cell, the clinical implications were obvious. But we're not there yet, although we did actually find the stem cells in human eyes as well as in mice. They're very hardy and viable, even a long time after death. You can do a lot to them and they still survive."
Van der Kooy foresees that "every important eye disease involving either the neural retina or the retinal pigment epithelium - parts of the eye that come from the brain - in principle could be susceptible to treatment with the stem cell. That applies in particular to macular degeneration and retinitis pigmentosa. It's a reasonable thing to think about for the future."
With a view to that future, van der Kooy and his co-authors are now studying mouse models of retinitis pigmentosa. "It's a good one to work on," he observed, "because photoreceptors are the most frequent cells on the eye, and degenerate in retinitis pigmentosa. We know that our stem cells can produce a lot of photoreceptors, so we're going into mouse models of that disease, to see if we can activate the stem cells."
He described two approaches: "One is to take the stem cells out, grow them in vitro, make a lot of photoreceptors, then put them back in the eye. That may be the short-term solution, but the long-term solution is to use the same techniques and growth factors that make the stem cells make photoreceptors in a dish, and put them in the eye - get the cell to do it in the eye, without surgery and transplants.
"The Frankenstein-like future farther down the road," van der Kooy envisioned, "is a pill, that will release the inhibition on the stem cell, get it to proliferate. Another part of the pill will cause it to make photoreceptors, and another part, to migrate to the place in the retina that's missing photoreceptors, and integrate them.
"But you can imagine," he allowed, "a lot of steps must be understood before we have a tool like that."
Meanwhile, van der Kooy said, "Within the past few months, the university has been granted U.S., Canadian and international patent allowances on its broad claims covering methods for the isolation of stem cells, and their transplantation and activation in the human eye. We're in negotiation with a whole bunch of commercial companies right now," he concluded. "We have a relationship with University Medical Discoveries Inc. in Toronto, and they've given us some seed money for this project."
Why Viagra Doesn't Work For Everybody Investigated In Mouse In Vivo Experiments
Sildenafil is not exactly a household word. It's the chemical name for Viagra, which needs no definition. That's the drug that brought the term erectile dysfunction out of the medical dictionary into public currency.
Premarket clinical testing of Viagra by its maker, Pfizer Inc., and subsequent wide acceptance have confirmed Viagra's efficacy in overcoming the physical and psychosomatic causes of a flaccid penis, unable to penetrate its vaginal objective, for sexual satisfaction or procreation.
Increased flow of arterial blood, natural or drug-assisted, inflates the two parallel columns of spongy corpus cavernosum tissue in the penis to the point of hard rigidity. Uncoiling of these helicine penile arteries, and simultaneous shutting off of venous blood outflow, depends on nitric oxide (NO). This activates a complex molecular pathway based largely on cyclic guanosine monophosphate (cGMP).
A Swedish research paper in the Feb. 29, 2000, issue of the Proceedings of the National Academy of Sciences (PNAS) points out, "A few patients with erectile dysfunction do not respond to sildenafil, suggesting they may have a functional disturbance of the NO/cGMP signaling cascade." The article is titled: "Erectile dysfuntion in cyclic GMP-dependent kinase I-deficient mice."
Stem-Cell Progenitor Cells Restored Circulation To Limbs Of Mice Modeling Human Ischemia
Reduced blood flow - ischemia - to feet and legs is a frequent cause of amputation in long-time diabetes sufferers. Researchers at Tufts University School of Medicine in Boston transplanted human endothelial progenitor cells into nude mice with hindlimb ischemia. This treatment "markedly improved" blood flow, and reduced limb loss. Their in vivo experiment, reported in the Proceedings of the National Academy of Sciences (PNAS), dated March 28, 2000, bears the title: "Transplantation of ex vivo expanded endothelial progenitor cells for therapeutic neovascularization."