Can Parkinson’s disease cause visual problems?

Eye test
We were working with G2019S – one of the most common Parkinson’s-related mutations. In fact, this mutation affects approximately 10 per cent of Parkinson’s patients. We were astonished to find how severe the visual defects were in the flies with this common form of the disease.
Dr Chris Elliott
Researchers from the University of York have linked a common Parkinson’s-related mutation to visual deterioration in an animal model. Using electroretinagram (ERG) technology, the team, whose research has been published in the journal Human Molecular Genetics, discovered an association between the presence of this mutant gene and a gradual loss of function in the eye nerve cells of fruit flies.

Parkinson’s is the second most common neurodegenerative disease after Alzheimer’s. Whilst the condition is predominantly associated with tremor and a slowness of movement, many patients with the disease have reported problems with their vision. In collaboration with colleagues from the University’s Centre for Chronic Disease and Disorders (C2D2), the York-based biologists are the first to successfully identify a genetic link – albeit within fruit flies – between Parkinson’s disease and visual deterioration.

To find out more about the implications of these findings, I spoke to the project’s lead researcher Dr Chris Elliott, Lecturer at the University of York’s Department of Biology. I began by asking about the severity with which this genetic mutation typically affects eyesight.

"It is a really hard question to answer," Dr Elliott responded. "As far as I understand, some Parkinson’s patients find it particularly difficult to adjust to sudden changes in light intensity. For example, if such a patient is driving along and a car travelling in the opposite direction dazzles them with bright headlights, they might find it difficult to cope with the rapid transition from dark to bright and back to dark. On the other hand, there are patients for whom this situation doesn’t appear to be very problematic."

For more than a century, scientists have used the common fruit fly, Drosophila, as a tool to broaden their understanding of human genetics. Indeed, Dr Elliott, whose research was partly funded by the charity Parkinson’s UK, says that the insect offers an ideal model on which to conduct quick and informative experiments.

"Patients reported experiencing similar visual difficulties even before anybody knew about the causes of Parkinson’s disease," he said. "Around a decade ago, the scientific community started to associate specific genes with Parkinson’s disease. We began to recognise Parkinson’s as an inherited condition. Because people and flies possess similar levels of dopamine within their visual systems, we reasoned that we would be able to use the insects to conduct experiments broadly applicable to humans.

"For these reasons, we had expected Drosophila to provide a good experimental model for our research," Dr Elliott continued. "We were working with G2019S – one of the most common Parkinson’s-related mutations. In fact, this mutation affects approximately 10 per cent of Parkinson’s patients. We were astonished to find how severe the visual defects were in the flies with this common form of the disease."

I asked Dr Elliott whether he has confidence that his findings will translate over to humans who possess the mutation. The strong correlations that exist between the visual systems of humans and fruit flies, he contends, mean that similar results are likely to be obtained from human-based studies in the future.

"I am quite confident that in due course, our results will be confirmed within humans," he said. "The eyes of flies and humans are surprisingly similar from an anatomical perspective. The main difference is that the fly’s eye is sitting on the surface of the insect and can be accessed very easily, whereas the human eye is behind a lens and therefore difficult to study. Even so, at a basic level, the same sorts of structure and nerve cell can be found in both. I am absolutely convinced that studies of human patients with Parkinson’s will reveal similar results to ours."

Last week, the University of Manchester’s Dr Andreas Prokop spoke to about the training package that he has created in a bid to encourage budding geneticists to utilise Drosophila within their research. Dr Elliott, who was well aware of Dr Prokop’s work, agrees that the fruit fly is an excellent tool for those working within the field of neurodegenerative disease.

"Drosophila is a wonderful animal model because it has been used by researchers for such a long period of time," he explained. "We know all sorts about fruit flies and they are excellent subjects for experimentation. For instance, if you’ve identified a mutation associated with a particular disease, you can introduce it into a fly in a way that would not be possible with a human. You can study the flies’ brains in exquisite detail. You can observe which nerve cells are growing and you can test to see whether or not they respond to particular stimuli. The fruit fly is a wonderful experimental organism."

Dr Elliott and his colleagues hope that their findings will facilitate clinicians attempting to manage Parkinson’s-related visual problems. I asked how a deeper understanding of the disease’s potential to affect eyesight might benefit patients suffering from such symptoms.

"When I first proposed this study to Parkinson’s UK, one respondent told me that as a person with the disease who had encountered similar visual problems, it was good to know that their experience was not unique," Dr Elliott replied. "Firstly, therefore, I think that it will be reassuring for Parkinson’s patients to know that they aren’t alone in experiencing visual difficulties. Clinicians need to recognise this issue as something to look for in certain groups of people. It is a symptom associated with Parkinson’s disease and should not be dismissed as unimportant. Secondly, we are trying to find out how flies with this mutation respond to different drugs used in the treatment of Parkinson’s. Our investigations are still at an early stage and we haven’t yet reached any conclusions, but we hope to have identified some of the most effective drugs before too long."

Finally, I asked Dr Elliott whether it might be possible – based on the presence or absence of this genetic mutation – for clinicians to identify patients most at risk of developing visual problems before they manifest themselves.

"Yes, it might," he concluded. "In fact, some of the data in our paper suggest that visual problems tend to appear long before movement defects manifest themselves. At least in fruit flies, these defects seem to arise before other problems associated with degeneration of the brain. This mutation might therefore represent a good marker in relation to the progress of Parkinson’s disease."



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