Targeted X-Ray Treatment of Mice Prevents Glaucoma

Researchers have demonstrated that a single, targeted X-ray treatment of a single eye in young, glaucoma-prone lab mice provided that eye with apparently life-long and typically complete protection from glaucoma.

In research published March 19, 2012, in the Journal of Clinical Investigation, Gareth Howell, PhD, Simon John, PhD, a professor at the Jackson Laboratory (Bar Harbor, ME, USA), and colleagues also used advanced genomics applications to discover some of the very first pathways to change during glaucoma in these mice. The first pathway they identified to change suggests a critical process that could be responsible for the earliest damage that glaucoma inflicts on the optic nerve.

Glaucoma, a leading cause of blindness, affects more than four million people in the United States alone, at least half of whom do not even know they have the disease. Current treatments target intraocular pressure elevation, the best-known risk factor for glaucoma. However, blindness-inducing damage to retinal ganglion cells and the optic nerve can occur in patients with normal intraocular eye pressure. Earlier detection and better treatments could therefore have a powerful impact on preventing blindness due to glaucoma.

Approximately a decade ago, the John lab made the remarkable discovery that just a single dose of whole-body irradiation along with bone marrow transfer conferred an unprecedented protection against glaucoma. Ninety-six percent of treated eyes had no glaucoma a year later compared to only 20% of control eyes.

Although this result was unexpected, there is some evidence that radiation may protect from human glaucoma. Epidemiologists who tracked Japanese survivors of the atomic bombings in World War II had noticed that exposure to radiation increased the incidence of thyroid and other cancers but seemed to provide protection against glaucoma.

The John labs’ new demonstration that irradiation of just one eye is protective, and at lower doses than they previously published, raises the possibility of using very controlled localized radiation of just the eye to prevent human glaucoma.

Further research in other animal models to assess protection as well as safety and effectiveness is necessary before attempting human treatments. However, as the authors concluded in their article, “Given both the robust and long-term efficacy of a single dose of X-ray radiation in preventing cellular entry into the optic nerve and retina, it will be important to further evaluate the use of X-rays for preventing glaucoma.”

The study demonstrated that in response to early tissue stresses, a type of immune cells called monocytes, enter the optic nerve and retina in glaucoma. These monocytes express damaging molecules that appear critical for nerve damage in glaucoma. The entry of these cells is controlled in part by endothelial cells that line blood vessels. Radiation treatment appears to change how these endothelial cells respond to the early tissue stresses and affect the entry of the monocytes into the optic nerve and retina.

“While more work is needed to fully understand how the radiation confers long-term protection,” Dr. Howell said, “radiation appears to hinder the adhesion and migration of monocytes into the areas of the eye prone to nerve damage.” This finding strongly implicates the entry of cells into the eye as a key component of the nerve damage that leads to blindness. It also suggests vision may be maintained in eyes with high intraocular pressure by treatments that block the entry of monocytes into the eye.

The Jackson Laboratory is an independent, nonprofit biomedical research institution and US National Cancer Institute (Bethesda, MD, USA)-designated cancer center based in Bar Harbor, Maine, with a facility in Sacramento, CA, USA, an institute for genomic medicine planned in Farmington, CT, USA, and a total staff of approximately 1,400. Its goal is to uncover the genetic basis for preventing, treating, and curing human disease, and to enable research and education for the global biomedical community.

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