{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T01:09:34Z","timestamp":1792631374369,"version":"4.5.0"},"reference-count":65,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2019,4,26]],"date-time":"2019-04-26T00:00:00Z","timestamp":1556236800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81400430"],"award-info":[{"award-number":["81400430"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"DOI":"10.3389\/fimmu.2019.00912","type":"journal-article","created":{"date-parts":[[2019,4,26]],"date-time":"2019-04-26T11:04:48Z","timestamp":1556276688000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":27,"title":["Microglia Mediate Synaptic Material Clearance at the Early Stage of Rats With Retinitis Pigmentosa"],"prefix":"10.3389","volume":"10","author":[{"given":"Juncai","family":"He","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Congjian","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaman","family":"Dai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuan Huang","family":"Weng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bai Shi Jiao","family":"Bian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Gong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingling","family":"Ge","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yajie","family":"Fang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haiwei","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zheng Qin","family":"Yin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2019,4,26]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1795","DOI":"10.1016\/S0140-6736(06)69740-7","article-title":"Retinitis pigmentosa","volume":"368","author":"Hartong","year":"2006","journal-title":"Lancet"},{"key":"B2","first-page":"11949","article-title":"NGL-2 regulates pathway-specific neurite growth and lamination, synapse formation, and signal transmission in the retina","volume-title":"J Neurosci.","author":"Soto","year":"2013"},{"key":"B3","first-page":"525","article-title":"Functional changes in inner retinal neurons in animal models of photoreceptor degeneration","volume-title":"Adv Exp Med Biol.","author":"Puthussery","year":"2010"},{"key":"B4","first-page":"5492","article-title":"Morphological and functional abnormalities in the inner retina of the rd\/rd mouse","volume-title":"J Neurosci.","author":"Strettoi","year":"2002"},{"key":"B5","first-page":"1057","article-title":"Early changes in synaptic connectivity following progressive photoreceptor degeneration in RCS rats","volume-title":"Eur J Neurosci.","author":"Cuenca","year":"2005"},{"key":"B6","doi-asserted-by":"publisher","first-page":"2071","DOI":"10.1002\/cne.22322","article-title":"Progression of neuronal and synaptic remodeling in the rd10 mouse model of retinitis pigmentosa","volume":"518","author":"Phillips","year":"2010","journal-title":"J Comp Neurol"},{"key":"B7","first-page":"222","article-title":"Retinal organization in the retinal degeneration 10 (rd10) mutant mouse: a morphological and ERG study","volume-title":"J Comp Neurol.","author":"Gargini","year":"2007"},{"key":"B8","doi-asserted-by":"publisher","first-page":"698","DOI":"10.1016\/j.neuroscience.2008.06.042","article-title":"Functional and structural modifications during retinal degeneration in the rd10 mouse","volume":"155","author":"Barhoum","year":"2008","journal-title":"Neuroscience"},{"key":"B9","first-page":"87","article-title":"Pathogenesis of retinal dystrophy in the Royal College of Surgeons rat","volume":"23","author":"Davidorf","year":"1991","journal-title":"Ann Ophthalmol"},{"key":"B10","first-page":"395","article-title":"Synaptic remodeling of neuronal circuits in early retinal degeneration","volume-title":"Front Cell Neurosci.","author":"Soto","year":"2015"},{"key":"B11","first-page":"461","article-title":"Physiology of microglia","volume-title":"Physiol Rev.","author":"Kettenmann","year":"2011"},{"key":"B12","doi-asserted-by":"publisher","first-page":"691","DOI":"10.1016\/j.neuron.2012.03.026","article-title":"Microglia sculpt postnatal neural circuits in an activity and complement-dependent manner","volume":"74","author":"Schafer","year":"2012","journal-title":"Neuron"},{"key":"B13","doi-asserted-by":"publisher","first-page":"1456","DOI":"10.1126\/science.1202529","article-title":"Synaptic pruning by microglia is necessary for normal brain development","volume":"333","author":"Paolicelli","year":"2011","journal-title":"Science"},{"key":"B14","first-page":"14","article-title":"Early events in retinal degeneration caused by rhodopsin mutation or pigment epithelium malfunction: differences and similarities","volume-title":"Front Neuroanat.","author":"Di Pierdomenico","year":"2017"},{"key":"B15","doi-asserted-by":"publisher","first-page":"1479","DOI":"10.1002\/glia.23016","article-title":"Microglial phagocytosis and activation underlying photoreceptor degeneration is regulated by CX3CL1-CX3CR1 signaling in a mouse model of retinitis pigmentosa","volume":"64","author":"Zabel","year":"2016","journal-title":"Glia"},{"key":"B16","first-page":"1179","article-title":"Microglial phagocytosis of living photoreceptors contributes to inherited retinal degeneration","volume-title":"EMBO Mol Med.","author":"Zhao","year":"2015"},{"key":"B17","first-page":"463","article-title":"Activated microglia in human retinitis pigmentosa, late-onset retinal degeneration, and age-related macular degeneration","volume-title":"Exp Eye Res.","author":"Gupta","year":"2003"},{"key":"B18","first-page":"30","article-title":"Retinal microglia: just bystander or target for therapy?","volume-title":"Prog Retin Eye Res.","author":"Karlstetter","year":"2015"},{"key":"B19","first-page":"8139","article-title":"Suppression of microglial activation is neuroprotective in a mouse model of human retinitis pigmentosa","volume-title":"J Neurosci.","author":"Peng","year":"2014"},{"key":"B20","doi-asserted-by":"publisher","first-page":"2992","DOI":"10.1167\/iovs.05-0118","article-title":"Identification of sequential events and factors associated with microglial activation, migration, and cytotoxicity in retinal degeneration in rd mice","volume":"46","author":"Zeng","year":"2005","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"B21","first-page":"45","article-title":"Microglia in the retina: roles in development, maturity, and disease","volume-title":"Ann Rev Vis Sci.","author":"Silverman","year":"2018"},{"key":"B22","first-page":"2506","article-title":"Structural and functional remodeling in the retina of a mouse with a photoreceptor synaptopathy: plasticity in the rod and degeneration in the cone system","volume-title":"Eur J Neurosci.","author":"Specht","year":"2007"},{"key":"B23","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1017\/S095252380623102X","article-title":"The nob2 mouse, a null mutation in Cacna1f: anatomical and functional abnormalities in the outer retina and their consequences on ganglion cell visual responses","volume":"23","author":"Chang","year":"2006","journal-title":"Vis Neurosci"},{"key":"B24","first-page":"1079","article-title":"Essential role of Ca2+-binding protein 4, a Cav1","volume-title":"Nat Neurosci.","author":"Haeseleer","year":"2004"},{"key":"B25","first-page":"270","article-title":"Mutations in MERTK, the human orthologue of the RCS rat retinal dystrophy gene, cause retinitis pigmentosa","volume-title":"Nat Genet.","author":"Gal","year":"2000"},{"key":"B26","doi-asserted-by":"publisher","first-page":"240","DOI":"10.1038\/nature17630","article-title":"TAM receptors regulate multiple features of microglial physiology","volume":"532","author":"Fourgeaud","year":"2016","journal-title":"Nature"},{"key":"B27","first-page":"1011","article-title":"Functional ectopic neuritogenesis by retinal rod bipolar cells is regulated by miR-125b-5p during retinal remodeling in RCS rats","volume-title":"Sci Rep.","author":"Fu","year":"2017"},{"key":"B28","doi-asserted-by":"publisher","first-page":"712","DOI":"10.1126\/science.aad8373","article-title":"Complement and microglia mediate early synapse loss in Alzheimer mouse models","volume":"352","author":"Hong","year":"2016","journal-title":"Science"},{"key":"B29","first-page":"7651","article-title":"Glutamatergic synapse formation is promoted by 7-containing nicotinic acetylcholine receptors","volume-title":"J Neurosci.","author":"Lozada","year":"2012"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.3791\/2270","article-title":"Quantifying synapses: an immunocytochemistry-based assay to quantify synapse number","volume":"45","author":"Ippolito","year":"2010"},{"key":"B31","doi-asserted-by":"publisher","first-page":"657","DOI":"10.1126\/science.291.5504.657","article-title":"Control of synapse number by glia","volume":"291","author":"Ullian","year":"2001","journal-title":"Science"},{"key":"B32","doi-asserted-by":"crossref","DOI":"10.3791\/51482","article-title":"An engulfment assay: a protocol to assess interactions between CNS phagocytes and neurons","volume-title":"J Visual Exp.","author":"Schafer","year":"2014"},{"key":"B33","first-page":"3546.7","article-title":"Improved retinal function in RCS rats after suppressing the over-activation of mGluR5","volume-title":"Sci Rep.","author":"Dai","year":"2017"},{"key":"B34","doi-asserted-by":"publisher","first-page":"813","DOI":"10.1016\/S0306-4522(03)00153-2","article-title":"Ectopic synaptogenesis during retinal degeneration in the royal college of surgeons rat","volume":"119","author":"Peng","year":"2003","journal-title":"Neuroscience"},{"key":"B35","first-page":"2693","article-title":"Apoptosis leads to photoreceptor degeneration in inherited retinal dystrophy of RCS rats","volume-title":"Invest Ophth Vis Sci.","author":"Tso","year":"1994"},{"key":"B36","first-page":"1789","article-title":"Neuronal integrity and complement control synaptic material clearance by microglia after CNS injury","volume-title":"J Exp Med.","author":"Norris","year":"2018"},{"key":"B37","first-page":"979","article-title":"The microglial innate immune receptor TREM2 is required for synapse elimination and normal brain connectivity","volume-title":"Immunity.","author":"Filipello","year":"2018"},{"key":"B38","doi-asserted-by":"publisher","first-page":"1265","DOI":"10.1093\/brain\/aww016","article-title":"Eliminating microglia in Alzheimer's mice prevents neuronal loss without modulating amyloid-\u03b2 pathology","volume":"139","author":"Spangenberg","year":"2016","journal-title":"Brain"},{"key":"B39","doi-asserted-by":"publisher","first-page":"380","DOI":"10.1016\/j.neuron.2014.02.040","article-title":"Colony-stimulating factor 1 receptor signaling is necessary for microglia viability, unmasking a microglia progenitor cell in the adult brain","volume":"82","author":"Elmore","year":"2014","journal-title":"Neuron"},{"key":"B40","first-page":"9","article-title":"The C1q complement family of synaptic organizers: not just complementary","volume-title":"Curr Opin Neurobiol.","author":"Yuzaki","year":"2017"},{"key":"B41","first-page":"24","article-title":"C1q propagates microglial activation and neurodegeneration in the visual axis following retinal ischemia\/reperfusion injury","volume-title":"Mol Neurodegener.","author":"Silverman","year":"2016"},{"key":"B42","first-page":"1007","article-title":"Complement C1q-C3-associated synaptic changes in multiple sclerosis hippocampus","volume-title":"Ann Neurol.","author":"Michailidou","year":"2015"},{"key":"B43","doi-asserted-by":"publisher","first-page":"2911","DOI":"10.1523\/JNEUROSCI.1136-17.2017","article-title":"Microglia-mediated synapse loss in Alzheimer's disease","volume":"38","author":"Rajendran","year":"2018","journal-title":"J Neurosci"},{"key":"B44","doi-asserted-by":"publisher","first-page":"2827","DOI":"10.1523\/JNEUROSCI.3575-15.2016","article-title":"Requirement for microglia for the maintenance of synaptic function and integrity in the mature retina","volume":"36","author":"Wang","year":"2016","journal-title":"J Neurosci"},{"key":"B45","doi-asserted-by":"publisher","first-page":"2039","DOI":"10.1167\/iovs.03-0741","article-title":"Morphological characterization of the retina of the CNGA3\u2212\/\u2212Rho\u2212\/\u2212 mutant mouse lacking functional cones and rods","volume":"45","author":"Claes","year":"2004","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"B46","first-page":"5","article-title":"Synaptogenesis and outer segment formation are perturbed in the neural retina of Crx mutant mice","volume-title":"BMC Neurosci.","author":"Morrow","year":"2005"},{"key":"B47","first-page":"594","article-title":"Neuronal remodeling in retinal circuit assembly, disassembly, and reassembly","volume-title":"Trends Neurosci.","author":"D Orazi","year":"2014"},{"key":"B48","first-page":"2423","article-title":"Photoreceptor ablation initiates the immediate loss of glutamate receptors in postsynaptic bipolar cells in retina","volume-title":"J. Neurosci.","author":"Dunn","year":"2015"},{"key":"B49","first-page":"1098","article-title":"How to make a synaptic ribbon: RIBEYE deletion abolishes ribbons in retinal synapses and disrupts neurotransmitter release","volume-title":"EMBO J.","author":"Maxeiner","year":"2016"},{"key":"B50","first-page":"6126","article-title":"Presynaptic dystroglycan-pikachurin complex regulates the proper synaptic connection between retinal photoreceptor and bipolar cells","volume-title":"J Neurosci.","author":"Omori","year":"2012"},{"key":"B51","first-page":"9399","article-title":"Disruption of laminin beta2 chain production causes alterations in morphology and function in the CNS","volume-title":"J Neurosci.","author":"Libby","year":"1999"},{"key":"B52","first-page":"67","article-title":"CNS synapses are stabilized trans-synaptically by laminins and laminin-interacting proteins","volume-title":"J Comp Neurol.","author":"Hunter","year":"2017"},{"key":"B53","first-page":"70","article-title":"Early apoptosis of rod photoreceptors in Rpe65(-\/-) mice is associated with the upregulated expression of lysosomal-mediated autophagic genes","volume-title":"Exp Eye Res.","author":"Metrailler","year":"2012"},{"key":"B54","first-page":"441","article-title":"Microglia function in the central nervous system during health and neurodegeneration","volume-title":"Annu Rev Immunol.","author":"Colonna","year":"2017"},{"key":"B55","first-page":"1773","article-title":"TGF-beta signaling regulates neuronal C1q expression and developmental synaptic refinement","volume-title":"Nat Neurosci.","author":"Bialas","year":"2013"},{"key":"B56","doi-asserted-by":"publisher","first-page":"7975","DOI":"10.1073\/pnas.0913449107","article-title":"Enhanced synaptic connectivity and epilepsy in C1q knockout mice","volume":"107","author":"Chu","year":"2010","journal-title":"Proc Natl Acad Sci U S A"},{"key":"B57","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1038\/nature16549","article-title":"Schizophrenia risk from complex variation of complement component 4","volume":"530","author":"Sekar","year":"2016","journal-title":"Nature"},{"key":"B58","doi-asserted-by":"publisher","first-page":"538","DOI":"10.1038\/nature18283","article-title":"A complement-microglial axis drives synapse loss during virus-induced memory impairment","volume":"534","author":"Vasek","year":"2016","journal-title":"Nature"},{"key":"B59","first-page":"26","article-title":"Inhibition of the classical pathway of the complement cascade prevents early dendritic and synaptic degeneration in glaucoma","volume-title":"Mol Neurodegener.","author":"Williams","year":"2016"},{"key":"B60","doi-asserted-by":"publisher","first-page":"8108","DOI":"10.1167\/iovs.10-6418","article-title":"Complement deposition and microglial activation in the outer retina in light-induced retinopathy: inhibition by a 5-HT1A agonist","volume":"52","author":"Collier","year":"2011","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"B61","first-page":"1596","article-title":"Microglia promote learning-dependent synapse formation through brain-derived neurotrophic factor","volume-title":"Cell.","author":"Parkhurst","year":"2013"},{"key":"B62","first-page":"3294","article-title":"Tamoxifen provides structural and functional rescue in murine models of photoreceptor degeneration","volume-title":"J Neurosci.","author":"Wang","year":"2017"},{"key":"B63","first-page":"6113","article-title":"Microglia are irrelevant for neuronal degeneration and axon regeneration after acute injury","volume-title":"J Neurosci.","author":"Hilla","year":"2017"},{"key":"B64","first-page":"5248","article-title":"Synaptic plasticity in CNGA3(-\/-) mice: cone bipolar cells react on the missing cone input and form ectopic synapses with rods","volume-title":"J Neurosci.","author":"Haverkamp","year":"2006"},{"key":"B65","doi-asserted-by":"publisher","first-page":"4635","DOI":"10.1523\/JNEUROSCI.2570-16.2017","article-title":"Deafferented adult rod bipolar cells create new synapses with photoreceptors to restore vision","volume":"37","author":"Beier","year":"2017","journal-title":"J Neurosci"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/article\/10.3389\/fimmu.2019.00912\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,4,26]],"date-time":"2019-04-26T11:05:16Z","timestamp":1556276716000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/article\/10.3389\/fimmu.2019.00912\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,4,26]]},"references-count":65,"alternative-id":["10.3389\/fimmu.2019.00912"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2019.00912","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,4,26]]},"article-number":"912"}}