Validation of retinal imaging for characterizing alpha-synuclein-eGFP deposition in a transgenic mouse model of Parkinson’s Disease/Dementia with Lewy Bodies

Abnormal accumulation of alpha-synuclein has been hypothesized to underlie neuronal cell death and synaptic dysfunctional leading to motor and cognitive symptoms in synucleinopathies such as Parkinson’s Disease (PD), Dementia with Lewy Bodies (DLB), and Multiple Systems Atrophy (MSA). Transgenic mouse models with overexpression of alpha-synuclein have proved useful in characterizing the behavioral, neuropathological, and biochemical consequences of alpha-synuclein aggregation. Nonetheless, the identification of truly translatable biomarkers relevant for therapeutic evaluations has proved difficult and is the focus of large scale collaborative efforts e.g., the Parkinson’s Progression Markers Initiative (PPMI). Retinal imaging can provide a non-invasive means to evaluate optical pathology (fundal maps and optical coherence tomography of vasculature and fluorescent-tagged proteins), and there is mounting evidence that ophthalmic pathology mirrors neuropathological processes of the central nervous system. In an effort to evaluate the presence and progression of retinal pathology in transgenic mouse models of PD/DLB, we conducted retinal imaging studies of mice overexpressing fused alpha-synuclein-GFP under the PDGF-beta promoter (PDNG78 line). Retinal imaging revealed perivascular and nerve terminal green fluorescent protein (GFP) labeling in transgenic, but not non-transgenic, PDNG78 mice. These observations correlate with central nervous system (CNS) observations in this same mouse line, which demonstrates the utility and relevance of retinal imaging by bright field and fluorescent studies for in vivo characterization of transgenic mouse model phenotypes as well as therapeutic evaluations.