Alzheimer's Protein Implicated in Glaucoma
TUESDAY Aug. 7, 2007 -- The same protein fragments that form plaques in the brains of people with Alzheimer's disease appear to cause the death of retinal cells in glaucoma, the potentially blinding eye disease, British researchers report.
In animal studies, drugs that blocked key molecular pathways for the protein fragments -- called amyloid-beta -- reduced eye damage and preserved the lives of retinal cells, said lead researcher Dr. M. Francesca Cordeiro, assistant professor of retinoneural degeneration at University College London.
Several methods of blocking those molecular pathways were tried in tests of rats bred to develop glaucoma, she explained.
"Just one treatment has prolonged the lives of retinal cells," Cordeiro noted. "Combining all the treatments together had a greater effect."
Confirmation of the eye-damaging role of amyloid-beta in further studies could open the way to new treatments for glaucoma, a leading cause of blindness in the United States.
It might also solve a puzzle that has led to a recent and revolutionary change in how ophthalmologists view the condition.
Until only a few years ago, glaucoma was officially described as the death of retinal cells caused by abnormally high pressure of the fluid in the eye. Even today, treatment is typically aimed at reducing this intraocular pressure.
But there has been growing awareness that a large percentage of glaucoma patients, perhaps more than half, have normal or near-normal intraocular pressure. In fact, the American Academy of Ophthalmology has removed mention of intraocular pressure as the cause of glaucoma and now describes pressure as just a major risk factor.
One of the clues pointing toward a causal role for amyloid-beta was the discovery of glaucoma-like retinal cell death in people with Alzheimer's disease, Cordeiro said. Laboratory work also revealed an accumulation of amyloid-beta in dying retinal cells, and adding the protein to cultured retinal cells induced their death.
"This is a very powerful idea," Cordeiro said. "We are really lacking non-pressure [based] treatments in glaucoma. Our research also gives an opportunity for treatment of Alzheimer's disease, using eyes as an entry point to the body."
The findings are published in this week's issue of the Proceedings of the National Academy of Sciences.
The basic idea behind the newly reported work is sound, said Dr. Stuart J. McKinnon, associate professor in ophthalmology and neurobiology at Duke University, in Durham, N.C. He has also performed studies that have implicated amyloid-beta in glaucoma.
Still, McKinnon sounded a note of caution. "We have to be a little careful in interpreting their conclusion," the Duke expert said. "Unfortunately, there is no good low-pressure animal model of glaucoma, so they used a rat model of increased intraocular pressure."
But, he added, "the conclusion that amyloid-beta is a major player in glaucoma is a sound one."
The amyloid-beta work "offers a potential mechanism that is not related to intraocular pressure, but what actually triggers retinal cell death is still not well understood," McKinnon said. "Are there genetic differences? Are different people more sensitive to intraocular pressure?"
In any event, the way is now open to new treatments aimed squarely at amyloid-beta, McKinnon said.
Someday, experts said, that might even include a vaccine that would be injected into the eye to prevent formation of the dangerous protein plaques.
Glaucoma and its medical management are described by the U.S. National Eye Institute.
Posted: August 2007