title: Requirement for Microglia for the Maintenance of Synaptic Function and Integrity in the Mature Retina.
abstract: Microglia, the principal resident immune cell of the CNS, exert significant influence on neurons during development and in pathological situations. However, if and how microglia contribute to normal neuronal function in the mature uninjured CNS is not well understood. We used the model of the adult mouse retina, a part of the CNS amenable to structural and functional analysis, to investigate the constitutive role of microglia by depleting microglia from the retina in a sustained manner using genetic methods. We discovered that microglia are not acutely required for the maintenance of adult retinal architecture, the survival of retinal neurons, or the laminar organization of their dendritic and axonal compartments. However, sustained microglial depletion results in the degeneration of photoreceptor synapses in the outer plexiform layer, leading to a progressive functional deterioration in retinal light responses. Our results demonstrate that microglia are constitutively required for the maintenance of synaptic structure in the adult retina and for synaptic transmission underlying normal visual function. Our findings on constitutive microglial function are relevant in understanding microglial contributions to pathology and in the consideration of therapeutic interventions that reduce or perturb constitutive microglial function.
  
  
  CONCLUSIONS
  Microglia, the principal resident immune cell population in the CNS, has been implicated in diseases in the brain and retina. However, how they contribute to the everyday function of the CNS is unclear. Using the model of the adult mouse retina, we examined the constitutive role of microglia by depleting microglia from the retina. We found that in the absence of microglia, retinal neurons did not undergo overt cell death or become structurally disorganized in their processes. However, connections between neurons called synapses begin to break down, leading to a decreased ability of the retina to transmit light responses. Our results indicate that retinal microglia contribute constitutively to the maintenance of synapses underlying healthy vision.
authors.affiliation: Unit on Neuron-Glia Interactions in Retinal Disease.
authors.forename: Xu
authors.initials: X
authors.lastname: Wang
authors.affiliation: Unit on Neuron-Glia Interactions in Retinal Disease.
authors.forename: Lian
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Synaptic Physiology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Biological Imaging Core.
authors.forename: Robert N
authors.initials: RN
authors.lastname: Fariss
authors.affiliation: Unit on Neuron-Glia Interactions in Retinal Disease.
authors.forename: Wenxin
authors.initials: W
authors.lastname: Ma
authors.affiliation: Retinal Circuit Development and Genetics Unit.
authors.forename: Friedrich
authors.initials: F
authors.lastname: Kretschmer
authors.affiliation: Unit on Neuron-Glia Interactions in Retinal Disease.
authors.forename: Minhua
authors.initials: M
authors.lastname: Wang
authors.affiliation: Visual Function Core, National Eye Institute, and.
authors.forename: Hao Hua
authors.initials: HH
authors.lastname: Qian
authors.affiliation: Retinal Circuit Development and Genetics Unit.
authors.forename: Tudor C
authors.initials: TC
authors.lastname: Badea
authors.affiliation: Synaptic Physiology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892.
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Diamond
authors.affiliation: Skirball Institute, Department of Neuroscience and Physiology, New York University School of Medicine, New York, New York 10016, and.
authors.forename: Wen-Biao
authors.initials: WB
authors.lastname: Gan
authors.affiliation: Centre d'Etude et de Recherche Thérapeutique en Ophtalmologie Retina France, and Paris-Saclay Institute of Neuroscience, CNRS, Université Paris-Sud, Université Paris-Saclay, 91405 Orsay, France.
authors.forename: Jerome E
authors.initials: JE
authors.lastname: Roger
authors.affiliation: Unit on Neuron-Glia Interactions in Retinal Disease, wongw@nei.nih.gov.
authors.forename: Wai T
authors.identifier: http://orcid.org/0000-0003-0681-4016
authors.initials: WT
authors.lastname: Wong
mesh_terms: D000818:Animals; D016923:Cell Death / Q000235:genetics; D004195:Disease Models, Animal; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism; D005136:Eye Proteins / Q000378:metabolism; D005260:Female; D015870:Gene Expression / Q000235:genetics; D005786:Gene Expression Regulation / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D017628:Microglia / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000502:physiology*; D017120:Nystagmus, Optokinetic / Q000235:genetics; D022661:RNA, Untranslated / Q000235:genetics / Q000378:metabolism; D023062:Receptors, Interleukin-8A / Q000235:genetics / Q000378:metabolism; D012160:Retina / Q000166:cytology*; D013569:Synapses / Q000235:genetics / Q000502:physiology*; D014786:Vision Disorders / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D014795:Visual Pathways / Q000502:physiology
chemical_list: D050483:Dopamine Plasma Membrane Transport Proteins; D005136:Eye Proteins; C110853:Gt(ROSA)26Sor non-coding RNA, mouse; D009419:Nerve Tissue Proteins; D022661:RNA, Untranslated; D023062:Receptors, Interleukin-8A
keywords: degeneration; electroretinogram; glia; microglia; retina; synapse