title: Longitudinal live imaging of retinal α-synuclein::GFP deposits in a transgenic mouse model of Parkinson's Disease/Dementia with Lewy Bodies.
abstract: Abnormal α-synuclein (α-syn) accumulation in the CNS may underlie neuronal cell and synaptic dysfunction leading to motor and cognitive deficits in synucleinopathies including Parkinson's disease (PD) and Dementia with Lewy Bodies (DLB). Multiple groups demonstrated α-syn accumulation in CNS accessory structures, including the eyes and olfactory terminals, as well as in peripheral organs of Parkinsonian patients. Retinal imaging studies of mice overexpressing fused α-syn::GFP were conducted to evaluate the presence and progression of retinal pathology in a PD/DLB transgenic mouse model. Bright-field image retinal maps and fluorescent images were acquired at 1-month intervals for 3 months. Retinal imaging revealed the accumulation of GFP-tagged α-syn in retinal ganglion cell layer and in the edges of arterial blood vessels in the transgenic mice. Double labeling studies confirmed that the α-syn::GFP-positive cells were retinal ganglion cells containing α-syn. Accumulation of α-syn persisted in the same cells and increased with age. Accumulation of α-syn::GFP was reduced by immunization with single chain antibodies against α-syn. In conclusion, longitudinal live imaging of the retina in the PDGF-α-syn::GFP mice might represent a useful, non-invasive tool to monitor the fate of α-syn accumulation in the CNS and to evaluate the therapeutic effects of compounds targeting α-syn.
authors.affiliation: Neuropore Therapies, Inc., CA 92121, San Diego, USA.
authors.forename: Diana L
authors.initials: DL
authors.lastname: Price
authors.affiliation: Department of Neurosciences, University of California, La Jolla, CA 92093, San Diego, USA.
authors.forename: Edward
authors.initials: E
authors.lastname: Rockenstein
authors.affiliation: Department of Neurosciences, University of California, La Jolla, CA 92093, San Diego, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Mante
authors.affiliation: Department of Neurosciences, University of California, La Jolla, CA 92093, San Diego, USA.
authors.forename: Anthony
authors.initials: A
authors.lastname: Adame
authors.affiliation: Department of Neurosciences, University of California, La Jolla, CA 92093, San Diego, USA.
authors.forename: Cassia
authors.initials: C
authors.lastname: Overk
authors.affiliation: Department of Neurosciences, University of California, La Jolla, CA 92093, San Diego, USA.
authors.forename: Brian
authors.initials: B
authors.lastname: Spencer
authors.affiliation: Department of Ophthalmology, University of California, La Jolla, CA 92093, San Diego, USA.
authors.forename: Karen X
authors.initials: KX
authors.lastname: Duong-Polk
authors.affiliation: Neuropore Therapies, Inc., CA 92121, San Diego, USA.
authors.forename: Douglas
authors.initials: D
authors.lastname: Bonhaus
authors.affiliation: Department of Ophthalmology, University of California, La Jolla, CA 92093, San Diego, USA.
authors.forename: James
authors.initials: J
authors.lastname: Lindsey
authors.affiliation: Department of Neurosciences, University of California, La Jolla, CA 92093, San Diego, USA.|Department of Pathology, University of California, La Jolla, CA 92093, San Diego, USA.
authors.forename: Eliezer
authors.initials: E
authors.lastname: Masliah
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D018450:Disease Progression; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007167:Immunotherapy; D020961:Lewy Body Disease / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000628:therapy; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D061848:Optical Imaging / Q000295:instrumentation; D010300:Parkinson Disease / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000628:therapy; D011993:Recombinant Fusion Proteins / Q000187:drug effects / Q000378:metabolism; D012160:Retina / Q000000981:diagnostic imaging* / Q000378:metabolism; D012165:Retinal Ganglion Cells / Q000378:metabolism; D057127:Single-Chain Antibodies / Q000008:administration & dosage* / Q000494:pharmacology; D051844:alpha-Synuclein / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*
chemical_list: D011993:Recombinant Fusion Proteins; D057127:Single-Chain Antibodies; D051844:alpha-Synuclein; D049452:Green Fluorescent Proteins