Parkinson's disease (PD) is a neurodegenerative condition characterised by the progressive deterioration of a type of neurons, called dopaminergic neurons, in the central autonomic and peripheral nervous system. This deterioration is due to the accumulation within the cytoplasm of the neurons of a protein, theα-synuclein (α-syn) badly folded. L' α-synuclein is an abundant presynaptic brain protein whose aggregation and misfolding have been identified among the critical factors in numerous neurodegenerative diseases. The causes of the accumulation of α-syn in the case of Parkinson's are still not entirely clear, as PD is probably a multifactorial disease, in which there is a mixture of genetic and environmental causes.
Parkinson's disease affects between 7 and 10 million people worldwide and typical symptoms of the disease include tremors, rigidity and bradykinesia (i.e. the slowing down of voluntary movements, such as walking, which become difficult to control) and a range of non-motor symptoms, including visual symptoms. The latter are present in almost 80% of patients with PD and include deficits in visual acuity and contrast sensitivity, and impaired colour vision.
The visual deficit appears to arise years before the onset of motor symptoms and reflects the course of the disease in the brain. The retina, by virtue of its similarity to brain tissue (since they both develop from the same embryonic tissue), is an excellent site for analysing the histopathological changes of PD that occur in the brain. Indeed, numerous studies in animal and human models of the disease have shown the presence of α-synuclein in retinal tissue, which could provide a means for the early and non-invasive diagnosis of Parkinson's disease, even before the onset of motor symptoms.
L'α-synuclein in the human retina
Many studies observed the accumulation of different forms of α-syn in the retina, as well as in brain tissue, although it is still unclear whether the visual symptoms of the disease are linked to this accumulation. However, recent studies seem to have found evidence that overexpression of α-syn in the retina is capable of leading to neurodegeneration of retinal cells in the eye, with a direct effect on visual functions such as light adaptation and visual acuity. These are mostly studies conducted in animal models and, therefore, further research in humans will be needed to better characterise and understand the mechanisms by which these pathological accumulations of α-syn influence the transmission of the visual impulse. A critical point for this research is the current possibility of observing the retina in vivo using imaging techniques.
DEarly iagnosis of PD: a possible help from SD-OCT
In this regard, SD-OCT (Spectral-Domain-Optical Coherence Tomography) is an imaging technology that allows the assessment of the retina in vivo, providing high-resolution information on retinal morphology and thickness values of the various areas of the retina. It is a non-invasive imaging technique and therefore an ideal tool for the assessment of retinal degenerative changes.
In patients with Parkinson's disease, in whom a retinal accumulation of alpha-synuclein has been hypothesised, SD-OCT may allow the accurate study of retinal layers, enabling the assessment of changes in structure or thickness, related to the disease. However, to date, there are still no solid studies in this regard. Further research will be needed to better characterise the changes in retinal architecture in the MoP revealed by SD-OCT in order to correlate them with the presence of α-syn and neuro-functional characteristics (visual acuity, contrast sensitivity and transmission of the visual impulse within the retina). For now, it has been possible to observe the indirect effects of what happens at the microscopic level; the next frontier will be to directly visualise intraretinal accumulations of α-syn in vivo, even before they start inducing retinal damage, so as to facilitate early diagnosis of the disease.
Observations and future developments
In conclusion, numerous studies have shown the accumulation of α-syn in different retinal localisations in Parkinson's disease. These observations have enormous potential to lay the foundations for a better understanding of the mechanisms by which visual impairment occurs in this disease and to develop the possibility of an early, non-invasive diagnosis of Parkinson's disease from the retina, even years before the onset of motor symptoms. For this to happen, however, retinal imaging techniques are needed to directly observe the effects of intraretinal accumulation of α-syn in vivo. The data on SD-OCT currently available are not yet sufficient for this purpose, although this technique and its further development in the future could enable the desired results in the early diagnosis of Parkinson's disease to be achieved.
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