Funded Studies
Objective/Rationale:
Although not usually thought of as part of Parkinson’s disease (PD), relatively subtle changes in vision and retinal structure have been reported among PD patients by multiple research groups. None of these differences, however, appear to be consistent or specific enough to serve as a diagnostic marker of PD. Dopamine neurons, whose degeneration in the brain cause much of PD patients’ disability, and alpha-synuclein, the protein that accumulates to form the characteristic Lewy bodies of PD, are both present in retinal cells, and, therefore, there is a possibility that detection of either of these might form the basis of a diagnostic eye test for PD.
Project Description:
This project is a pilot study that would quickly assess the potential of the two most likely retinal PD biomarkers: dopaminergic loss and pathological alpha-synuclein accumulation. The retinas from the eyes of autopsied PD and non-PD subjects will be stained to produce microscopic slides that will be analyzed for the abundance of dopaminergic nerve cells and for pathological accumulation of alpha-synuclein.
Relevance to Diagnosis/Treatment of Parkinson’s Disease:
Currently, the accuracy of the diagnosis of PD during life varies from about 60 percent, within the first few years of symptoms, to 85 percent, after several years of symptoms, medical observation and treatment. The poor clinical accuracy of PD during the early phase of the disease is a major roadblock to finding effective new treatments to prevent or slow the disease before it progresses to major disability. A retinal biomarker of PD would potentially allow an accurate early diagnosis of PD through a specialized eye examination.
Anticipated Outcome:
The project will determine the potential usefulness of retinal dopaminergic nerve cell degeneration and/or alpha-synuclein accumulation for forming the basis of a diagnostic eye test for PD. By comparing the abundance of retinal dopaminergic nerve cells in PD and non-PD subjects, and by assessing for the presence or absence of alpha-synuclein accumulation in PD retinas, we will establish whether there is enough promise to warrant development of a specialized eye test to detect these changes in living PD subjects.
Final Outcome
Staining with some antibodies, including the staining done for dopaminergic nerve cells, has so far been too inconsistent to provide reliable information. A manuscript describing the findings with the phosphorylated alpha-synuclein (p-syn) antibody has been submitted to the rapid publication journal Neuroscience Letters. P-syn-positive nerve fibers were present in 7/9 PD subjects and in one PD subject there were some entire p-syn-positive neurons; there were also positive fibers in 1/3 subjects with dementia with Lewy bodies. There were no stained nerve fibers or other specific staining in any of the non-PD subjects. It is possible that at least some of the observed visual function impairments in PD subjects might be due to alpha-synucleinopathy and that the psyn-positive fibers might allow an ophthalmological diagnostic test for PD should appropriate technology be developed for this. Analysis of the retinas stained with the GFAP antibody, a marker of non-specific neural degeneration, is currently underway in the laboratory of a collaborator we have recruited, Dr. Nicolas Cuenca of the Universidad de Alicante, Alicante, Spain. Dr. Cuenca is a retinal histology expert. Analysis of the retinas stained with the dopaminergic neuronal marker may still be possible, and we will attempt this, although the analysis will likely be limited in its conclusions due to the variability in staining.
June 2014