Researchers found that certain mutations enable specific cells in the retina to multiply and cause eye cancer, a finding that suggests deliberate genetic manipulations might coax an injured brain to repair itself
MEMPHIS, Tenn., Oct. 18 /PRNewswire-USNewswire/ -- Investigators at St. Jude Children's Research Hospital have identified the cell that gives rise to the eye cancer retinoblastoma, disproving a long-standing principle of nerve growth and development. The finding suggests for the first time that it may one day be possible for scientists to induce fully developed neurons to multiply and coax the injured brain to repair itself.
A report of this work appears in the Oct. 19 issue of the journal "Cell." Michael Dyer, Ph.D., an associate member in the St. Jude Department of Developmental Neurobiology, is the report's senior author.
The immediate importance of the St. Jude finding is that it unexpectedly showed that retinoblastoma can arise from fully matured nerves in the retina called horizontal interneurons. This disproves the scientific principle that fully formed, mature nerves cannot multiply like young, immature cells, Dyer said. Human neurodegenerative disorders such as Alzheimer's disease can occur when differentiated nerves in the brain try to multiply, and in the process, trigger a self-destruct program called apoptosis. Differentiation is the process by which cells lose their primitive, stem-cell-like properties that include the ability to grow and multiply, and instead develop specialized shapes and functions.
The St. Jude researchers showed that when the activity of the Rb family of genes was reduced in the retina of mouse models, fully differentiated horizontal neurons could multiply and yet retain all of the differentiated features of normal horizontal neurons including neurites and synapses.
"For the past 100 years, it's been ingrained among scientists that differentiated mature nerves are so elaborate that they can't divide, and if they try to divide, they undergo cell death," Dyer said. "This is the first time that anyone has shown that under certain conditions, a fully mature and differentiated nerve can undergo cell division and multiply."
The discovery that fully differentiated horizontal interneurons can multiply to form retinoblastoma also challenges the established scientific belief that cancer cells are most aggressive when they are undifferentiated, Dyer said. For example, the leukemic cells of chronic myelogeneous leukemia (CML) are much less aggressive when they are differentiated; and it is generally not aggressive until the tumor cells sustain mutations that block differentiation.
An important implication of this finding is that if researchers were able to alter the activity of certain genes in fully developed neurons, they might be able to trigger them to multiply temporarily and replace the neighboring neurons that were lost as a result of neurodegenerative diseases such as Alzheimer's, Dyer said. "Having nerves duplicate themselves might be more efficient than trying to stimulate nerve replacement by inserting stem cells into the brain, since the existing nerves would already be in the right place to restore missing brain cells," he said. "However, there is still a lot of research required to determine if it is possible to control gene activity to make this approach practical."
Other authors of this paper include Itsuki Ajioka, Rodrigo A. P. Martins, Ildar T. Bayazitov, Stacy Donovan, Samantha Cicero, Kelli Boyd and Stanislav S. Zakharenko (St. Jude); Dianna A. Johnson (University of Tennessee Health Science Center, Memphis) and Sharon Frase (University of Memphis).
This work was supported in part by the National Institutes of Health, the National Cancer Institute, the American Cancer Society, Research to Prevent Blindness, Pearle Vision Foundation, the International Retinal Research Foundation, the Whitehall Foundation, NARSAD (The Mental Health Research Association) and ALSAC. Dyer is a Pew Scholar; Zakharenko is a Searle Scholar.
St. Jude Children's Research Hospital
St. Jude Children's Research Hospital is internationally recognized for its pioneering work in finding cures and saving children with cancer and other catastrophic diseases. Founded by late entertainer Danny Thomas and based in Memphis, Tenn., St. Jude freely shares its discoveries with scientific and medical communities around the world. No family ever pays for treatments not covered by insurance, and families without insurance are never asked to pay. St. Jude is financially supported by ALSAC, its fundraising organization. For more information, please visit http://www.stjude.org.
|SOURCE St. Jude Children's Research Hospital|
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