University of Michigan Kellogg Eye Center | 1000 Wall Street, Ann Arbor, MI 48105 | 734.763.8122
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| Retinal stem cells in Fish: nature’s way of healing vision
Dr. Hitchcock began his research on the teleost—or bony—fish some 20 years ago. He and his colleagues have demonstrated that these fish possess “intrinsic” stem cells, a finding that could help us understand more about the potential of stem cells in treating disorders of the nervous system, first in animal models, and eventually in humans. Among the more dramatic possibilities is that of transplanting cells capable of generating new tissue to heal injuries to the retina or central nervous system. Dr. Hitchcock explains that fish harbor these retinal stem cells as a consequence of the way they grow. As a fish grows, from very small to sometimes very large, its brain and retina make new neurons from neuronal precursors that reside within the brain. What’s most striking, in the retina when existing neurons are destroyed, new ones are regenerated. “The capacity for self renewal and the ability to reconstitute a tissue are the classical definitions of a stem cell,” says Dr. Hitchcock. “We know that stem cells reside in the retinas of fish, and therein lies the value of studying this animal. The fish does naturally what medicine would like to do therapeutically.” An evolutionary trait that scientists would like to replicate The uncanny ability of a fish to make new neurons continually and repair its brain most likely relates to a characteristic called “indeterminate growth,” says Dr. Hitchcock. This means that fish have no genetic endpoint to their growth as do most mammals. For example, the zebra fish grows to a mere two inches, yet by the time it reaches maturity, it will have increased its mass roughly a million times over that at hatching. According to Dr. Hitchcock, “It would be logistically impossible to pack into a tiny hatchling fish all the brain cells needed in the adult. These animals have evolved a mechanism to keep generating neurons as they grow.” And as fish grow, their eyes increase in size as well, resulting in a fine-tuned optical instrument with an ever-increasing number of neurons. By comparison, humans grow only modestly after birth, reaching a relatively predictable size, increasing in mass only about 20 times from birth to maturity. “More to the point, before birth we humans produce nearly all the neurons needed throughout life,” says Dr. Hitchcock. “The comparatively large size of the newborn’s eyes and head reflect the fact that they house a lifetime’s supply of neurons.” Stem cells in fish as a model for human healing Fish have served as a useful model for studying neurogenesis—generating neural cells—in part, because they create new neurons at a vigorous rate that is easy to observe. Some cells in the fish retina are dedicated to making rod photoreceptors, the light-sensitive cells responsible for night vision. Yet when an injury occurs these cells switch gears. They halt the production of rods and regenerate retinal neurons of all types. Scientists know that neural stem cells also exist in the brains of mammals, including humans. Although replication is much less vigorous in mammals than in fish, it appears that the persistent neurogenesis in both animals relies on the same basic biological principles. It is not yet clear what stem cells in the brains of mammals are meant to do, though some scientists believe they may be related to memory or to a modest level of replacement of neurons that have died. Dr. Hitchcock’s study of neurogenesis in fish is important because the process is similar to that in the human nervous system. He points out that vertebrate retinas—including humans and fish—share a similar anatomy and physiology. Knowledge about retinal regeneration in fish could reveal principles that will guide scientists’ ability to transplant stem cells into human retinas. Currently, Dr. Hitchcock and his colleagues are trying to identify the genes that regulate the production of new retinal neurons under normal conditions and during regeneration following an injury. Says Dr. Hitchcock, “Identifying the gene is just the beginning, because that allows you to move on to the really interesting biological questions— how these genes function, which cells express them, and what roles they play in retinal repair.” Dr. Hitchcock likens his work as a scientist to finding tiny pieces of a very large puzzle, knowing that he has made a little progress each day. Recent discoveries in genetics and in decoding the human genome have led some to say that this is “the century of the biologist.” For Dr. Hitchcock and his colleagues at Kellogg, the interesting biological questions about teleost fish may lead to new discoveries in stem cell research and, ultimately, to new ways to heal and treat vision disorders. Peter Hitchcock’s research is funded, in large part, by the National Eye Institute. |
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University of Michigan Kellogg Eye Center | 1000 Wall Street, Ann Arbor, MI 48105 | 734.763.8122
Copyright © Regents of the University of Michigan |