Friday January 15 2010
Could the windows to the soul warn of ill health?
The Daily Mirror says there could be a “high street eye test for Alzheimer's” within five years. The newspaper says that new research in mice has shown that placing a harmless fluorescent dye into the retina of the eye could identify dying nerve cells, which are an early sign of Alzheimer's.
The model developed in this study is a novel way of studying the death of eye nerve cells in living animals. This research mainly tested whether the technique could detect cell death in the retinas of rodents, including in animals with rodent versions of the human diseases glaucoma and Alzheimer’s. However, it did not test whether the technique could effectively distinguish between different diseases in animals or what the results can tell us about the health of nerve cells in the brain.
Diagnosing Alzheimer’s disease is complicated, and additional tests to help identify the condition would be useful. While this technique merits further research, it is too soon to say that the test might be successful in humans or can be used to single out Alzheimer’s disease as a cause of someone’s symptoms.
Where did the story come from?
This research was conducted by Professor Francesca Cordeiro and colleagues from University College London and other research centres in the US and Italy. The study was funded by The Wellcome Trust and The Foundation Fighting Blindness. Some of the study’s authors are named as inventors on a patent application covering the technology described in the study. The study was published in the open-access peer-reviewed journal Cell Death and Disease.
The Daily Telegraph, Daily Mirror and BBC News all report on this story. They all state that the research is in mice, and that human trials will follow. Their coverage is generally accurate. The Mirror and BBC News suggest that the test could be available in five years, while The Telegraph suggests it could be as soon as two years. However, it is too early to predict how soon this test might be available, as it is not yet clear whether it would be useful, safe or even possible in humans.
What kind of research was this?
This was animal research looking at whether researchers could detect the death of nerve cells in living rats and mice as it happened. Nerve-cell death is a key feature of diseases such as Alzheimer’s and glaucoma. It is not yet possible to detect nerve-cell death in the brain while it is occurring. In this study the researchers tested a system for looking at nerve-cell death in the retina of the eye. Because of similarities between nerve-cell death in the eye and in the brain, they hoped that this technique might give insight into brain nerve-cell death.
This initial stage of experimentation could not be performed in humans, but it can provide a clearer picture of whether this new technique might work in humans. However, it will take much further research to determine how the technique might be successfully used in humans.
Although the newspapers have highlighted the technique’s potential for diagnosing Alzheimer’s disease, nerve-cell death occurs in the brain in various neurological and eye diseases, including Parkinson’s and glaucoma. In its current form, this technique would only be useful in detecting neurological diseases where there is nerve-cell death in the eye. Another challenge for the researchers developing this technique would be ensuring that this test would be able to distinguish between different conditions that cause nerve-cell death in the eye.
What did the research involve?
The researchers have developed a technique for identifying dying nerve cells in the retinas of live anaesthetised rodents over hours, days and weeks. They used fluorescent dyes that will only attach to cells that are dying, making them glow when exposed to certain wavelengths of light. These dyes can also distinguish between different ways in which cell death can occur, and whether a cell is in the early or late stages of dying.
They then used this technique to look at the way eye nerve cells were affected by different chemicals that either cause or prevent the death of nerve cells. They first injected the eyes of rats with a chemical called staurosporine that is known to cause nerve-cell death. This injection also included the fluorescent dyes that would attach to dying nerve cells. They then shone specific wavelengths of light into the eye and used time-lapse video to watch what happened in the retina.
The researchers then repeated their experiment using an injection of amyloid beta, instead of staurosporine, into the eyes of mice. Amyloid beta is a protein that builds up in the brain cells in people with Alzheimer’s disease and in the retinas of people with glaucoma. When injected in the eyes of rodents, it causes nerve-cell death in the retina. Research has also shown that amyloid beta accumulates in the retinas of mice genetically engineered to have a condition similar to Alzheimer’s disease.
The researchers also tested whether they could detect a reduction in nerve-cell death when they injected the eyes with a nerve-protecting chemical called MK801 at the same time as the amyloid beta.
Finally, the researchers used their technique to look at eye nerve-cell death in rodent models of chronic disease. They used a rat model of glaucoma and a genetically engineered mouse model of Alzheimer’s disease.
What were the basic results?
The researchers tested their technique and found that they could detect individual nerve cells dying in the retinas of rats and mice whose eyes had been injected with staurosporine or amyloid beta. The level of detail observable also meant that they could identify the type and pattern of cell death occurring. They also showed that they could detect a reduction in cell death when a nerve-protecting chemical was injected into the eye at the same time as amyloid beta.
Nerve-cell death could also be detected in the retinas of a rat model of glaucoma and the genetically engineered mouse model of Alzheimer’s disease. A reduction in cell death was again observed when a nerve-protecting chemical was injected into the eye of the rat glaucoma model.
Slightly different patterns of cell death could be seen in the models of glaucoma and Alzheimer’s disease compared to the ‘acute models’, which had been produced by injecting staurosporine or amyloid beta. These acute models featured fewer cells in the late stages of death than the chronic models.
How did the researchers interpret the results?
The researchers concluded that the retina is an “ideal experimental model” that allows “monitoring of disease mechanisms and dynamics in experimental neurodegeneration”. They say that the equipment they used is “essentially the same” as equipment already used by hospitals and eye clinics, and that its availability raises the possibility that, in the near future, clinicians may be able to assess retinal-nerve-cell death in patients to monitor the progression of their disease and provide appropriate treatment.
The model developed in this study is a novel way of studying cell death in the retinas of living animal models and, as such, is likely to be a useful research tool. This study mainly tested whether the technique could detect cell death in the retinas of rodents, including in animal models of the human diseases glaucoma and Alzheimer’s disease. It did not focus on how well the technique could distinguish between different diseases in animals, or what the results of the test can tell us about the health of nerve cells in the brain.
Diagnosing Alzheimer’s disease is complicated, with diagnoses currently made on the basis of exclusion of other causes, characteristic clinical symptoms and brain-scan images that correspond to Alzheimer’s. Additional tests that can help with this diagnosis would be useful, but, given the experimental nature of this technique, it is too early as yet to say whether it will become useful in routine medical practice. Although it seems likely that this test could identify nerve-cell death in human eyes, we do not yet know whether it would be able to differentiate between healthy adults and people with Alzheimer’s disease, or other neurological or eye diseases.