title: Proteomic Profiling Suggests Central Role Of STAT Signaling during Retinal Degeneration in the rd10 Mouse Model.
abstract: The rd10 mouse is a model of retinitis pigmentosa characterized by the dysfunction of a rod-photoreceptor-specific phosphodiesterase. Compared to the rd1 mouse, retinal degeneration in the rd10 mouse begins later in age with a milder phenotype, making it ideal for investigating cell death and neuroprotective mechanisms. Alterations in the rd10 retina proteome at pre-, peak-, and postdegenerative time points were examined using a modified high-recovery filter-aided sample preparation (FASP) method in combination with label-free quantitative mass spectrometry, generating a proteomic data set on almost 3000 proteins. Our data confirmed a period of protein expression similar to age-matched wild-type mice predegeneration, with decreases in proteins associated with phototransduction and increases in signaling proteins at peak- and postdegenerative stages. A total of 57 proteins were differentially expressed in the rd10 retinae during peak-degeneration, compared to those in wild-type mice after stringent FDR correction (q < 0.05). Network analysis separated these proteins into one cluster of down-regulated photoreceptor proteins and one of up-regulated signaling proteins centered around GFAP, STAT3, and STAT1. This is the first study to identify alterations in STAT1 in the rd10 mouse, which were confirmed with gene expression and immunoblotting experiments, underpinning the efficacy of our approach. This unique proteomic data set on protein dynamics during retinal degeneration could serve as an information source for vision research in the future.
authors.affiliation: Research Unit Protein Science, Helmholtz Zentrum München, German Research Center for Environmental Health (GmbH) , Neuherberg, D-85764 Germany.|Research Unit Analytical Pathology, Helmholtz Zentrum München, German Research Center for Environmental Health (GmbH) , Neuherberg, D-85764 Germany.
authors.forename: Alice
authors.initials: A
authors.lastname: Ly
authors.affiliation: Research Unit Protein Science, Helmholtz Zentrum München, German Research Center for Environmental Health (GmbH) , Neuherberg, D-85764 Germany.
authors.forename: Juliane
authors.initials: J
authors.lastname: Merl-Pham
authors.affiliation: Research Unit Protein Science, Helmholtz Zentrum München, German Research Center for Environmental Health (GmbH) , Neuherberg, D-85764 Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Priller
authors.affiliation: Research Unit Protein Science, Helmholtz Zentrum München, German Research Center for Environmental Health (GmbH) , Neuherberg, D-85764 Germany.
authors.forename: Fabian
authors.initials: F
authors.lastname: Gruhn
authors.affiliation: Research Unit Protein Science, Helmholtz Zentrum München, German Research Center for Environmental Health (GmbH) , Neuherberg, D-85764 Germany.
authors.forename: Nicole
authors.initials: N
authors.lastname: Senninger
authors.affiliation: Research Unit Protein Science, Helmholtz Zentrum München, German Research Center for Environmental Health (GmbH) , Neuherberg, D-85764 Germany.|Centre of Ophthalmology, Institute for Ophthalmic Research, University of Tübingen , Tübingen, 72076 Germany.
authors.forename: Marius
authors.initials: M
authors.lastname: Ueffing
authors.affiliation: Research Unit Protein Science, Helmholtz Zentrum München, German Research Center for Environmental Health (GmbH) , Neuherberg, D-85764 Germany.
authors.forename: Stefanie M
authors.initials: SM
authors.lastname: Hauck
mesh_terms: D000818:Animals; D016923:Cell Death; D002853:Chromatography, Liquid; D004195:Disease Models, Animal; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D025941:Protein Interaction Mapping; D020543:Proteome / Q000235:genetics / Q000378:metabolism*; D017948:Retinal Rod Photoreceptor Cells / Q000378:metabolism* / Q000473:pathology; D012174:Retinitis Pigmentosa / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D050794:STAT1 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D053719:Tandem Mass Spectrometry; D014785:Vision, Ocular
chemical_list: D005904:Glial Fibrillary Acidic Protein; D020543:Proteome; D050794:STAT1 Transcription Factor; D050796:STAT3 Transcription Factor; C494080:Stat1 protein, mouse; C494087:Stat3 protein, mouse; C528900:glial fibrillary astrocytic protein, mouse
keywords: eye; immunohistochemistry; label-free mass spectrometry; phospho-STAT; photoreceptor cell death; retinal Müller glial cells; retinitis pigmentosa