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Retinal Pathology in Parkinson’s Disease: Implications for Vision and Biomarkers

Study Rationale:                   
Vision problems are not what most of us think of when we think of Parkinson’s disease (PD), but there are some physical changes in the retina of people with PD, including an accumulation of the protein alpha-synuclein like that found in the PD brain. It has been suggested that this and/or other eye abnormalities might form the basis of clinical tests that could be used to help diagnose PD or assess whether some PD therapies are working. 

The primary hypothesis is that changes in the retina, including accumulation of alpha-synuclein and/or loss of dopaminergic neurons, will accurately identify people living with PD and that these changes will ultimately allow an ophthalmological diagnosis and assessment of PD severity.  

Study Design:
We were recently the first to report accumulation of alpha-synuclein in retinal nerve cells of people with PD. This finding needs to be tested in additional people with and without PD to be sure it is a reliable finding. We will also assess the dopaminergic nerve cells of the retina to determine if they are radically depleted, like the dopaminergic neurons in the PD brain. Furthermore, we will assess the overall degree of retinal damage by measuring retinal thickness and numbers of other types of retinal nerve cells, as well as the amount of glial “scar tissue” that is present.

Impact on Diagnosis/Treatment of Parkinson’s Disease:             
Although this study will use donated eyes from people with PD who have passed away, it is quite possible that the changes seen could potentially be used to improve the diagnosis of PD and to evaluate if PD treatments in development are working.

Next Steps for Development:
If this study confirms that certain eye changes are reliably and selectively present in people with PD, the next step would be to develop clinical eye tests that could detect these changes in people living with PD.

Final Outcome

People with Parkinson's disease (PD) have a number of visual impairments, including changes in contrast sensitivity, color vision, and object and motion processing deficits. We studied retinas of PD individuals to assess the molecular and morphological changes in order to find possible biomarkers of the disease that can be used as predictors.

Our results showed the presence of phosphorylated alpha-synuclein in the retina, in specific types of cells including cell bodies, dendrites and axons. A clear correlation between the amount of phosphorylated alpha-synuclein present in retina and in brain was observed, suggesting that the identification of this protein in the retina may be a useful biomarker for PD, if methods can be developed for detecting it during life.

Additionally, as in the brains of people with PD, we found a decrease in the numbers of dopamine cells and a reduction of their synaptic contacts with their postsynaptic neurons. We made a preliminary study of retinal glial cells that was suggestive of a possible inflammatory state. Finally, we found a definite decrease in the numbers, the ganglion cells, as well as the loss of their axons in the optic nerve, and these findings agree with some reports using in vivo retinal imaging methods.

As well as possibly being useful as biomarkers, these retinal changes may be responsible for some or all of the functional visual alterations in this disease.


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