$50,000 Prize to Glaucoma Researcher for Significant Discovery Regarding the Mechanism of Infantile Glaucoma
Simon W. M. John, Ph.D., Associate Investigator at the Howard Hughes Medical Institute at The Jackson Laboratory in Bar Harbor, Maine, received the prestigious $50,000 award this month in recognition of his significant contribution to understanding primary congenital glaucoma (PCG), which strikes 1 in 10,000 newborns in the United States. PCG often causes pain, corneal tears, and blindness at a young age. Treatments are limited and not always successful.
Researchers knew that a mutation of a gene called CYP1B1 was present in human PCG patients, but did not understand why only some babies with that mutation were born with PCG. It suggested that more than one gene causes the disease. "It was really a mystery why some people with the mutant gene were getting glaucoma and some were not," John said.
John and colleagues performed more than five years of studies on hundreds of genetically cross-bred mice who had the mutant CYP1B1 gene, and also had defective eye-drainage structures that are characteristic of infant glaucoma. "It was the mouse version of the same gene in humans," John said. Using a clever breeding approach, his team discovered that the drainage structure defects were even worse in mice with a second genetic mutation: that of the tyrosinase gene. Tyrosinase had never before been implicated in glaucoma, and this work suggests that it is worth testing in human glaucoma.
Knowing that tyrosinase makes L-dopa, a molecule involved in cell behavior, John and colleagues decided to test whether L-dopa influences proper drainage structure development in utero. They dissolved L-dopa into the drinking water of female mice that had both genetic mutations and had not yet mated. Mice continued to be fed the L-dopa water during pregnancy and after giving birth, while their pups suckled. This treatment almost entirely prevented drainage structure defects among the pups, even in the face of both genetic mutations.
"It's truly incredible - it's a rare thing in a lifetime you can discover something like that," John said.
The discovery of L-dopa's role in proper development of the eyes' drainage structure holds important potential implications for PCG treatment, said Dr. David H. Abramson, chairman of the Academy's Lewis Rudin Glaucoma Prize Committee. "It may explain the association between certain glaucomas and developmental anomalies and potentially opens an entirely new approach to the diagnosis and treatment of glaucoma," said Abramson, Chief of Ophthalmic Oncology Service at Memorial Sloan-Kettering Cancer Center and professor of Ophthalmology at Weill Cornell Medical College.
PCG results when the eyes' drainage structure does not form properly in utero. The structure completely encircles the eye, and is supposed to drain aqueous fluid that flows out of the eyeball. When this fluid is not adequately removed, eye pressure builds and causes nerve cell damage, which results in glaucoma. The developmental abnormalities that cause PCG are poorly understood, John explained. It was not clear that multiple genetic and/or environmental factors could affect occurrence of PCG, and perhaps interact to compromise the drainage structures to a greater degree.
John hopes that some day L-dopa or a similar drug can be ingested by women of childbearing age whose children are at risk of having PCG. This may protect their children against PCG, just as folic acid is taken to ward off spina bifida. L-dopa is already used to treat Parkinson's disease patients. But since it affects the nervous system, safety and proper dosing would have to be carefully determined before treatment could ever begin, in order to protect the fetus. "It would be wonderful if the mothers could just drink it, just as we did with the mice," John said.
The next step for John's lab will be to tailor the mouse experiments to administer different doses of L-Dopa, and to determine the most appropriate time of treatment. This is important because it may not be necessary to treat throughout pregnancy. Very defined treatment periods may have less risk for the fetus.
John describes winning the Rudin Prize as "a big thrill," and one that affirms the value of mouse studies in advancing understanding about the mechanisms behind glaucoma.
"When I started my lab nine years ago, and we were talking about using mice to study glaucoma, it really wasn't thought to be worthwhile by a number of people," John said. "Some people said mice were too different from people anatomically. The tide has turned, and mouse studies are becoming accepted throughout the community now."
"Our study demonstrates the real strengths of mouse genetics to lead us to the unexpected: things that you can't predict," he said.
The Academy awards the Rudin Prize annually for the most outstanding glaucoma research published during the previous year. Dr. John was senior author on a paper in the March 7, 2003 issue of the journal Science, entitled, "Modification of ocular defects in mouse developmental glaucoma models by tyrosinase." The Rudin Prize was established in 1995 and is funded by the May and Samuel Rudin Family Foundation, Inc. Recipients are chosen by an international selection committee and approved by the Academy Board of Trustees.
The study was predominantly supported by the Howard Hughes Medical Institute. The New York Academy of Medicine is a non-profit institution founded in 1847 that is dedicated to enhancing the health of the public through research education and advocacy with a particular focus on urban populations, especially the disadvantaged. Visit the Academy online at http://www.nyam.org.
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50000 dolari Premiul pentru glaucom Cercetãtor semnificative pentru Discovery În ceea ce priveºte mecanismul de infantil glaucom - $50,000 Prize to Glaucoma Researcher for Significant Discovery Regarding the Mechanism of Infantile Glaucoma - articole medicale engleza - startsanatate