Author:

Keywords:

alpha-synuclein, Parkinson’s disease, in vivo follow-up, retina

Abstract:

Although it is well-documented that many patients with Parkinson’s disease (PD) present with visual disabilities, scientific research has largely neglected the impact of PD on the retina. Nevertheless, a profound understanding of the retinal manifestations of PD would not only help to gain new insights into the pathogenesis of PD, it would also open up new avenues to improved disease management. In this study, we exploit the advantages of the retina - being the most accessible part of the central nervous system- as a model organ for CNS research. The aim of this study is to develop and characterize a novel mouse model for the study of PD in the retina, based on local, viral vector-mediated overexpression of α-synuclein (αSYN). In a pilot study, C57BL/6N mice were intravitreally injected in the right eye with an adeno-associated viral vector in order to overexpress αSYN in the retina. Efficient and homogenous transduction of the entire retina was achieved and resulted in αSYN overexpression in neurons in the ganglion cell layer and inner nuclear layer as soon as 2 weeks post injection. We observed retinal thinning starting from week 14 with optical coherence tomography (OCT). Confocal scanning laser ophthalmoscopy (cSLO) also revealed autofluorescent spots at that same time point, indicative of protein aggregation. Together, this indicates αSYN aggregation and neurodegeneration. The latter was also demonstrated when we tested visual function with a virtual optomotor system at that time point: reduced visual acuity was shown. Together, these results suggest that the retina can be used as a model organ to study the effect of (or the link between) α-synucleinopathy on neuronal survival. We are currently confirming this pilot data, and further characterizing this novel model using electrophysiology, cSLO and ‘detection of apoptosing retinal cells’ techniques. In further studies, we intend to validate this disease model as a screening tool to evaluate the impact of therapeutic interventions on PD disease progression.