Nerve Link: Alzheimer’s suspect shows up in glaucoma

A protein fragment that litters the brains of people with Alzheimer’s disease may also bear responsibility for some of the vision loss in glaucoma, a new study in rats shows.

Glaucoma patients typically have abnormal fluid pressure within the eye, but it remains unknown how this stress kills the nerve cells at the back of the retina. While there is no cure for glaucoma, easing eye pressure with drugs or surgery helps prevent vision loss in many patients.

Some glaucoma patients, however, experience vision loss even with normal eye pressure, indicating that other factors are sometimes involved.

The new research suggests that one hidden assailant is amyloid-beta, the same protein fragment that accumulates in the brains of Alzheimer’s patients. An earlier rodent study of glaucoma had found the substance in the animals’ eyes, but other evidence of amyloid-beta in glaucoma is scarce.

In the new study, ophthalmologist M. Francesca Cordeiro of University College London and her colleagues induced glaucoma in 60 rats by injecting saline into the animals’ eyes. Within weeks, amyloid-beta deposits showed up in dying retinal-nerve cells.

The researchers then gave another round of eye injections to some of the rats. In one eye, the animals received a synthetic antibody that absorbs amyloid-beta. The other eye got a placebo.

After 3 weeks, the medicated eyes showed only one-fourth as much retinal-cell death as did the untreated eyes, the researchers report in an upcoming Proceedings of the National Academy of Sciences. The effect remained 13 weeks later.

Next, the scientists repeated the experiment on other rats with glaucoma, this time using a cocktail that included the antibody and two other drugs with anti–amyloid-beta effects: a dye called Congo red and an enzyme deactivator called beta-secretase inhibitor. The triple combination worked even better than the antibody alone, reducing cell death by 84 percent.

“This offers a novel hypothesis and very intriguing results with the potential for therapeutic impact on a devastating, blinding disease,” says psychiatrist Lee E. Goldstein of Harvard Medical School and the Brigham and Women’s Hospital in Boston. It remains unclear, though, whether amyloid-beta is similarly involved in human glaucoma and, if so, whether it’s a perpetrator of the disease or a bystander. “The jury is still out,” says Goldstein.

Researchers are currently testing an amyloid-beta antibody as a drug in a large trial of Alzheimer’s patients, but Congo red and beta-secretase inhibitor haven’t entered that stage of Alzheimer’s testing, Cordeiro says. She says she’s hopeful that scientists will assess the triple combination in glaucoma patients within 2 or 3 years.

“One of the problems I have as a glaucoma doctor is that there are no other real treatments out there, other than reducing pressure in the eye,” she says.