title: In vivo imaging of retinal gliosis: a platform for diagnosis of PD and Screening of anti-PD compounds.
abstract: Parkinson's disease (PD) is the second most frequent degenerative disorder after Alzheimer's disease. It is characterized by the depletion of mesenchephalic dopaminergic (DA) neurons in the substantia nigra pars compacta (SNpc) and striatal dopamine. Oxidative stress plays a major role in the pathogenesis of Parkinson's disease where DA neurons are especially vulnerable to excessive production of the H2O2 reactive oxygen species. Unfortunately, the first clinical symptoms of PD occur after at least 60-80% of nigro-striatal dopaminergic neurons have lost their function. Therefore, early detection of PD is critical in slowing down the progression of the disease and enabling the development of therapeutic compounds which could intervene at an earlier stage. Here, we employ in vivo molecular imaging of astrocytic retinal gliosis in a transgenic mice to longitudinally monitor the progression of MPTP-induced PD. We have quantitatively evaluated, via this imaging platform, the efficacy of a synthetic antioxidant, 1,3- bisbenzylimidazolium bromide (DBZIM), in protecting the DA neurons and scavenging the ROS. We show here that MPTPinduced PD results in an upregulation of glial fibrillary acidic protein (GFAP), a marker for gliosis, by 36% relative to saline whereas gliosis is normalized in MPTP-induced PD mice treated with DBZIM.
authors.affiliation: Institute of Bioengineering and Nanotechnology, 31 Biopolis Way, Singapore 138669. skumar@ibn.a-star.edu.sg
authors.forename: S
authors.initials: S
authors.lastname: Kumar
authors.forename: G
authors.initials: G
authors.lastname: Ho
authors.forename: Y
authors.initials: Y
authors.lastname: Zhang
authors.forename: L
authors.initials: L
authors.lastname: Zhuo
mesh_terms: D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000494:pharmacology; D000818:Animals; D018450:Disease Progression; D015259:Dopamine Agents / Q000494:pharmacology; D005838:Genotype; D005904:Glial Fibrillary Acidic Protein / Q000737:chemistry; D005911:Gliosis / Q000473:pathology*; D049452:Green Fluorescent Proteins / Q000378:metabolism; D007093:Imidazoles / Q000494:pharmacology; D007150:Immunohistochemistry / Q000379:methods; D051379:Mice; D008822:Mice, Transgenic; D018384:Oxidative Stress; D010300:Parkinson Disease / Q000175:diagnosis* / Q000188:drug therapy / Q000473:pathology*; D017382:Reactive Oxygen Species; D012160:Retina / Q000473:pathology*
chemical_list: D015259:Dopamine Agents; D005904:Glial Fibrillary Acidic Protein; D007093:Imidazoles; D017382:Reactive Oxygen Species; D049452:Green Fluorescent Proteins; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine