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Targeting α-synuclein by PD03 AFFITOPE■ and Anle 138b rescues neurodegenerative pathology in a model of multiple system atrophy:clinical relevance

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Translational Neurodegeneration 2020年第3期9卷 484-497页

作者： Miguel Lemos Serena Venezia Violetta Refolo antonio heras-gavin Sabine Schmidhuber Armin Giese Andrei Leonov Sergey Ryazanov Christian Griesinger Gergana Galabova Guenther Safer Gregor Karl Wenning Nadia Stefanova Division of Neurobiology Department of NeurologyInnsbruck Medical University6020 InnsbruckAustria AFFIRIS AG ViennaAustria Center for Neuropathology and Prion Research Ludwig-Maximilians-UniversityMunichGermany Max Planck Institute for Biophysical Chemistry GottingenGermany Present Address:Origenis GmbH MunichGermany

Background:Misfolded oligomeric α-synuclein plays a pivotal role in the pathogenesis of a-synucleinopathies including Parkinson's disease and multiple system atrophy,and its detection parallels activation of microglia and a loss of neurons in the substantia nigra pars *** we aimed to analyze the therapeutic efficacy of PD03,a new AFFITOPE■ immunotherapy approach,either alone or in combination with Anle138b,in a PLP-α-syn mouse ***:The PLP-α-syn mice were treated with PD03 immunotherapy,Anle138b,or a combination of *** months after study initiation,the mice underwent behavioral testing and were sacrificed for neuropathological *** treatment groups were compared to the vehicle group with regard to motor performance,nigral neuronal loss,microglial activation and α-synuclein ***:The PLP-α-syn mice receiving the PD03 or Anle138b single therapy showed improvement of gait deficits and preservation of nigral dopaminergic neurons associated with the reduced α-synuclein oligomer levels and decreased microglial *** combined therapy with Anle138b and PD03 resulted in lower lgG binding in the brain as compared to the single immunotherapy with ***:PD03 and Anle138b can selectively target oligomeric α-synuclein,resulting in attenuation of neurodegeneration in the PLP-α-syn *** approaches are potential therapies that should be developed further for disease modification in α-synucleinopathies.

关键词： α-Synuclein Immunotherapy Oligomer modulation Target engagement Substantia nigra Microglia

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Fractal analysis of retinal vasculature in normal subjects on ultra-wide field fluorescein angiography

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International Journal of Ophthalmology(English edition) 2020年第7期13卷 1109-1114页

作者： Wen-Ying Fan Alan Fleming gavin Robertson Akihito Uji Jano van Hemert Michael Singer Min Sagong Michael Ip SriniVas R.Sadda Beijing Tongren Eye Center Beijing Tongren HospitalBeijing Ophthalmology and Visual Sciences Key LaboratoryCapital Medical UniversityBeijing 100730China Doheny Image Reading Center Doheny Eye InstituteLos AngelesCA 90086USA Department of Ophthalmology David Geffen School of Medicine at UCLALos AngelesCA 90095USA Optos PLC Dunfermline KY118GRUnited Kingdom Department of Ophthalmology Medical Center Ophthalmology AssociatesSan AntonioTX 78258USA

AIM: To evaluate the fractal feature of the retinal vasculature of normal eyes on a stereographic projected and montaged ultra-wide field(UWF) fluorescein angiography(FA).METHODS: Prospective, observational, cross-sectional study. Totally 59 eyes of 31 normal subjects were imaged using the Optos 200 Tx. Images obtained at different gaze angles stereographically projected and montaged. The early-phase UWF FA frames were processed to segment the retinal vasculature and the results were exported as binary masks. The fractal dimension(FD) was calculated using the box-counting ***: The global FD for the entire retina was 1.6±0.04, with no difference between males and females(1.59±0.04 vs 1.61±0.04, P=0.084) or between right and left eyes(1.6±0.04 vs 1.6±0.05, P=0.61). FD was nonuniformly distributed among four quadrants(P0.05).CONCLUSION: Fractal geometry is non-uniformly distributed across the retina in normal eyes and decreases from the fovea to the far-periphery. Subjects with an older age tend to have a smaller FD, however, the FD in the farperiphery does not appear to be influenced by age.

关键词： fractal analysis retina ultra-wide field fluorescein angiography normal subject

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