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Blocking neurodegeneration by radiation and bone marrow transfer prevents inherited glaucoma in mice


In a discovery that could point to new treatments for a wide range of neurodegenerative diseases, Jackson Laboratory researchers have found that high-dose radiation and bone marrow transfer treatments on glaucoma-susceptible mice completely blocked the development of glaucoma, by preventing neurodegeneration.

Glaucomas are among the most common neurodegenerative diseases, and a leading cause of blindness in the United States. Many patients with glaucoma have high intraocular pressure (IOP), long believed to be a cause of the degeneration of the optic nerve and nerve cells in the retina that leads to vision loss. The standard treatment for glaucoma is reducing the intraocular pressure by medication or surgery.

However, researchers have also observed that some patients with elevated IOP do not develop optic nerve and retinal damage, while others do incur damage despite relatively normal IOP. "It’s increasingly clear," says Dr. Simon W.M. John, leader of the Jackson Laboratory research team and a Howard Hughes Medical Institute Investigator, "that multiple mechanisms are at work in this disease."

John and researchers elsewhere have identified several genes associated with glaucomas. They have also developed inherited mouse glaucoma models that reliably develop glaucoma in mid-life. One of these models is the DBA/2J mouse.

The Jackson research team treated 5- to 8-week-old DBA/2J mice with a single, high dose of gamma radiation, together with bone marrow transfer.

When they examined the mice at 12-14 months--an age at which most DBA/2J mice have advanced glaucoma--the researchers were amazed to find that the vast majority of mice did not have glaucoma. There was no detectable loss of the retinal ganglion cells, which typically degenerate in glaucoma. "It was very surprising and we had to be very careful," John said. "We repeated the experiment two more times with the same results."

The research paper, published online in the Proceedings of the National Academy of Sciences, is the first to suggest that high-dose radiation together with bone marrow transfer--treatments in use today for human patients with leukemia and other cancers--could potentially treat glaucoma. "It is possible that the treatment may also protect against other neurodegenerative diseases, but many experiments are needed to test this," he noted. Conditions in this category include Alzheimer’s disease and Parkinson’s disease.

Of course, full-body radiation and bone marrow transfer is not an appropriate therapy for human glaucoma. Dr. John said his lab would be investigating whether directing radiation locally to the optic nerve and retina might be equally effective in preventing glaucoma in mice. Ultimately, studies that reveal how the treatment works may lead to new types of therapy for people.

The Jackson Laboratory, founded 75 years ago, is the world’s largest mammalian genetics research institution. Its research staff of more than 450 investigates the genetic basis of cancers, heart disease, osteoporosis, Alzheimer’s disease, glaucoma, diabetes, and many other human diseases and disorders. The Laboratory is also the world’s source for nearly 3,000 strains of genetically defined mice, home of the Mouse Genome Database and many other publicly available information resources, and an international hub for scientific courses, conferences, training and education.

Joyce Peterson | EurekAlert!
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