Parkinson’s disease is the second most common neurodegenerative disease after Alzheimer’s disease and today affects more than 5 million people worldwide. Although characterized primarily by movement disorders, its effects on the brain and body are much broader and can include vision problems, dementia, sleep and bowel problems.
One of the lead authors, Dr. Ching-Hwa Sung, an expert in stem cell research, biology and ophthalmology at Weill Cornell Medicine explains that the experiments conducted on this unique animal model ultimately reveal that removal of a key component involved in protein transport in photosensitive rods leads to retinal accumulation of alpha-synuclein aggregatesthis toxic accumulation being found in patients with Parkinson’s disease.
The study first enabled the development of these unique models of Parkinson’s disease, mice lacking a protein, VPS35, only in rod cells, the principal light-sensitive neurons of the retina. VPS35 is known to help cells deliver molecules to their corresponding destinations, including sending abnormal proteins for degradation. A mutation in the VPS35 gene has been associated with a familial form of Parkinson’s disease. Observations of this model reveal that:
- even in young mice, rods lacking VPS35 rapidly lose their synapses – connection points with other neurons – leading to visual impairment similar to that observed in patients with Parkinson’s disease;
- aggregates of alpha-synuclein – the toxic protein that accumulates in Parkinson’s disease – form and, eventually, as the affected rods begin to die, mouse retinas develop large inclusions similar to Lewy bodies, or alpha-synuclein aggregates;
- interactions of VPS35 with other proteins are also observed and reveal that VPS35 functions not only by removing aggregated alpha-synuclein, but also by preventing its aggregation.
The absence or elimination of the VPS35 protein thus induces powerful “Parkinson like” effects. The advantages of the new model include the ultra-rapid development of the pathological process, which can also make it possible to understand this process more quickly and to identify new markers or new therapeutic targets.
A new possible detection strategy, via analysis of the fundus of the eye : in these model mice, aged 3 months and with rod cells lacking VPS35, a standard ophthalmological device called a fundoscope makes it possible to observe, on the back of the eye, bright spots associated with alpha-synuclein aggregates. A clinical trial is already planned for this new screening approach.
In the end, it is a new model for studying the disease but also a promising diagnostic tool that is delivered to us here.
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