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Plasma Proteome Analysis on Cynomolgus Monkey (Macaca Fascicularis) Pedigrees with Early Onset Drusen Formation
Authors:Hiroaki Kobayashi  Haru Okamoto  Akira Murakami  Takeshi Iwata
Affiliation:1) Division of Molecular & Cellular Biology, National Institute of Sensory Organs, National Hospital Organization Tokyo Medical Center, 2-5-1 Higashigaoka, Meguro-ku, Tokyo 152-8902, Japan;2) Department of Ophthalmology, Juntendo University, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan
Abstract:The central region of the primate retina is called macula. The fovea is located at thecenter of the macula, where the photoreceptors are concentrated to create neural networkadapted for high visual acuity. Damage to the fovea by macular dystrophies and age-relatedmacular degeneration (AMD) can reduce the central visual acuity. The molecular mechanismsleading to these diseases are most likely dependent on the proteins in macula differ fromthat in peripheral retina in expression level. Previously, we reported an early onsetmacular degeneration with drusen in cynomolgus monkey pedigrees. These monkeys showsimilar fundus findings of early stage of AMD at 2 years after birth. To elucidatemechanism of drusen formation and to find disease biomarkers for early stage of AMD, weperformed plasma proteome analysis. Plasma samples were collected from four affected andcontrol monkeys within the same pedigree. Successful fractionation of the plasma proteinsby ProteoMiner and Gelfree8100 were confirmed by SDS-PAGE. Total of 245 proteins wereidentified from eight samples. From the results of spectral counting, we selected someproteins, Apolipoprotein E, Histidine-rich glycoprotein, and Retinol-binding protein 4 ascandidate proteins that would be related with drusen formation. Candidate proteins wouldbe potentially beneficial as biomarkers for human AMD. One of the identified proteins,Apolipoprotein E (ApoE), is structural component of drusen and also related with otherneurodegenerative disease like Alzheimer disease. In this plasma proteome analysis, ApoEwould be one of the possible factors of early drusen formation in these cynomolgus monkeypedigrees.
Keywords:age-related macular degeneration   drusen   mass spectrometry   plasma   proteome
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