Study finds link between Alzheimer’s and glaucoma

Both Alzheimer’s disease and glaucoma may be caused by the same mechanism, reported The Daily Telegraph on August 7 2007. The newspaper quoted the researchers, saying they had found “a clear link between what causes Alzheimer’s and one of the basic mechanisms behind glaucoma”.

BBC News quoted the researchers as saying “drugs which slow progress of Alzheimer’s disease may protect patients at risk of eye damage from glaucoma”. The Guardian reported that “the link between the two diseases suggests glaucoma may be used as an early warning sign of future Alzheimer’s”. 

The study is an animal study, which shows that beta-amyloid, a protein that forms large deposits or plaques in the brains of people with Alzheimer’s disease, may also be involved in the mechanism of glaucoma. Drugs that block the action of beta-amyloid were shown to reduce the death of particular cells in rat eyes with a glaucoma-like condition.

It is important not to make assumptions from an animal study as to how humans might benefit from this. This study provides insufficient evidence to change current practice in the treatment of glaucoma. It also gives no indication that people with either glaucoma or Alzheimer’s are at an increased risk of developing the other condition.

Where did the story come from?

Research was conducted by Li Guo and colleagues from University College London Institute of Ophthalmology, London, the Institute of Ophthalmology, University of Parma, Parma, Italy, Institut Cochin, Paris and the Glaucoma Research Group, London. It was published in the journal, Proceedings of the National Academy of Sciences .

What kind of scientific study was this?

This was a laboratory animal study, which artificially induced a glaucoma-like condition in rats to investigate the mechanism of development of glaucoma.   

The researchers initially marked particular cells in the eyes of the rats – retinal ganglion cells – with a molecule to allow them to be identified easily. Three groups of experiments were carried out, and after each experiment, imaging was used to look for the death of the eye cells. Cell samples were also examined under a microscope.

In the first experiment, the interior pressure of the left eye of each rat was increased to simulate glaucoma. This was done with an injection of saline solution into veins in the eyeball. The right eye was not touched and this served as a control for the study. The eyes were then imaged at 2, 3, 8, 12 and 16 weeks.

In the second experiment beta-amyloid was injected directly into the eyes of the rats. Imaging was then performed at 2, 6, 24, 48 and 72 hours.

In the third experiment, in the rats with increased interior eye pressure, different drugs which are known to target beta-amyloid were injected, either alone or in combination. Saline solution was used as a control. Imaging was performed at baseline, and 3, 8, and 16 weeks of the study.

What were the results of the study?

The interior pressure in the rat eyes was successfully raised in the first experiment, increasing over time up to 16 weeks. In the areas of the eye showing where there was cell death, there was an increase in the amount of beta-amyloid found.

After injecting beta-amyloid directly into the rat eyes in the second experiment, the rate of cell death increased, with the highest levels observed with the higher doses of beta-amyloid.

In the third experiment, in the rats with raised interior eye pressure, the drugs that targeted beta-amyloid were found to reduce the amount of cell death, with a combination of drugs being more effective than a single drug.

What interpretations did the researchers draw from these results?

The researchers concluded that beta-amyloid is implicated in the development of cell death in the eye in rats with an artificially-induced glaucoma-like condition. They suggest that a possible treatment for glaucoma is a drug that prevents beta-amyloid from acting on these cells in the eye.

What does the NHS Knowledge Service make of this study?

This research appears to be a good laboratory study, using quite complicated methods. However, there are many things to consider when interpreting both the results of this study and the newspaper reports, and the relationship to the development and current management of glaucoma, or to Alzheimer’s disease.

• The study involves tests in rats with an artificially induced glaucoma-like condition. It is not clear if the mechanism of cell death is the same in humans, or whether the drugs tested would act in a similar way in human eyes.
• The condition of glaucoma is complex, and we cannot interpret from this research that beta-amyloid alone causes the development of glaucoma. Glaucoma is usually associated with raised internal eye pressure, due to the fluid contained within the eye. This causes damage to the optic nerve at the back of the eye, and puts the patient at risk of visual loss. It is not possible to tell at this stage what the significance, if any, of beta-amyloid deposits are in this process. 
• Current treatment of glaucoma is targeted at reducing interior eye pressure through a variety of methods: using eye drops (e.g. beta blockers); tablets (drugs known as carbonic anhydrase inhibitors); or lastly laser or surgery to treat the meshwork that lies around the coloured part of the eye (iris) through which fluid normally circulates. There is insufficient evidence from this study to indicate any change in current practice; for example, some of the news reports suggest that Alzheimer’s drugs may be used in treatment.
• Importantly, the study neither investigates nor implies that people with glaucoma are at greater risk of developing Alzheimer’s disease than the general population, or that likewise people with Alzheimer’s may be at increased risk of glaucoma. The newspaper reports may lead you to believe that the two conditions are related; however, this is currently only speculation and a clear link has not been demonstrated.

Definitive conclusions about the role of beta-amyloid in the development or progression of glaucoma will only be able to be drawn when more animal and human studies have been carried out. Any potential treatment for glaucoma may take several years to develop.