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Glaucoma and Alzheimer's May Have Common Origins and Treatment

Submitted by dave on Tue, 08/07/2007 - 11:35am

This news comes from Neil Osterweil, Senior Associate Editor, MedPage Today. (Reviewed by Zalman S. Agus, MD; Emeritus Professor at the University of Pennsylvania School of Medicine.)

August 06, 2007

See (I have had trouble navigating directly to the link, however. You may have to visit the main page and then search for the article.)

I find the research on amyloid-beta very interesting from an Ayurvedic perspective. If you are familiar with the Ayurvedic concept of ama, you may have a sense of excitement about the possibility that the concept of ama encompasses amyloid-beta. This is exciting because Ayurveda has treatments for reducing ama.

Below is an excerpt from the article. While reading, keep in mind that studies of the Alzheimers drugs in glaucoma have only been done in rats and use in humans may be a long way off. (Of course, I also recommend you keep in mind that there may be Ayurvedic treatments of interest in connection with this research that you can pursue right now.)

A combination of drugs that target the amyloid-beta pathway implicated in Alzheimer's disease appear to be highly effective against glaucoma as well, at least in animal models, investigators here reported.
Action Points

Amyloid-b peptide, found to accumulate in the brains of people with Alzheimer's disease, accelerated the programmed death of retinal ganglion cells in rat models of glaucoma, but its action was prevented by three drugs that inhibit Ab formation and aggregation, wrote M. Francesca Cordeiro, M.D., of University College London, and colleagues.

The findings, published online in Proceedings of the National Academy of Sciences, suggest that blocking the action of amyloid-b peptide may offer a new method for slowing or preventing glaucoma progression.

"Perhaps the most exciting finding of the work has been that combination therapy, targeting three different aspects of the amyloid-b pathway, produced the maximal reduction of retinal ganglion cell apoptosis (>80%)," one of the earliest signs of glaucomatous neural damage, they wrote.

Although conventional glaucoma therapy -- both medication and surgery -- is aimed at lowering intraocular pressure, glaucoma can progress even when intraocular pressure is normal, indicating that other mechanisms may be at work, the authors noted.

"The principal step leading to irreversible loss of vision in glaucoma is retinal ganglion cell apoptosis, and the question is what mechanisms precede this cell death," they wrote.

Because amyloid-b has recently been implicated in the death of retinal ganglion cells, the authors conducted a series of four experiments to assess the relationship between the peptide and glaucomatous damage to ocular nerves.

They first looked at the association of amyloid-b with retinal ganglion cell apoptosis in rat models of glaucoma, in which elevated intraocular pressure is induced in one eye, with the other eye serving as a control.

They found that there was significant overlap of amyloid-b and apoptotic retinal ganglion cells, suggesting that the known neurotoxic effects of the peptide might also damage neurons in the optic pathway.

The researchers then injected two forms of amyloid-b into the vitreous humor of the eyes, and saw that the effect of the protein increased over time and higher doses of the most potently neurotoxic amyloid-b oligomer produced the highest degree of retinal ganglion cell die-off.

In the final two stages of their experiment, they looked at the effects of monotherapy and a combination of three drugs on the retinal ganglion cells.

The drugs include an inhibitor of b-secretase, an enzyme that cleaves the amyloid-precursor protein in the first step of abnormal amyloid-b deposition, Congo red, a dye that has been shown to completely block amyloid-b aggregation and neurotoxicity in hippocampal neurons of rats, and a monoclonal antibody directed against amyloid-b.

They found that overall, the anti-amyloid-b antibody appeared to be the most effective at preventing retinal ganglion cell apoptosis, with effects lasting up to 16 weeks, which may be because of a combined effect of the drug to both block amyloid-b action and prevent its aggregation.

"In comparison, Congo red dramatically reduced retinal ganglion cell apoptosis at three weeks and resulted in a delayed peak of retinal ganglion cell apoptosis at eight weeks after raised intraocular pressure," they wrote. "However, compared with the [antibody], Congo red appeared to have a shorter window of protection against retinal ganglion cell apoptosis."

The beta-secretase inhibitor did not significantly prevent, but did appear to at least delay the peak. This may have been related to the low dose used, the authors said, noting that there is evidence to suggest that beta-secretase inhibition may be an effective intervention in this setting.

When the authors tried the agents in combination, however, they hit the jackpot, observing a significantly improved neuroprotective effect after three weeks of increased intraocular pressure compared with the anti-amyloid-b antibody alone.

The triple therapy resulted in an 84% mean reduction of retinal ganglion cell apoptosis compared with a 74% reduction for the monoclonal antibody alone (P<0.05).

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