title: Retinal microglia: just bystander or target for therapy?
abstract: Resident microglial cells can be regarded as the immunological watchdogs of the brain and the retina. They are active sensors of their neuronal microenvironment and rapidly respond to various insults with a morphological and functional transformation into reactive phagocytes. There is strong evidence from animal models and in situ analyses of human tissue that microglial reactivity is a common hallmark of various retinal degenerative and inflammatory diseases. These include rare hereditary retinopathies such as retinitis pigmentosa and X-linked juvenile retinoschisis but also comprise more common multifactorial retinal diseases such as age-related macular degeneration, diabetic retinopathy, glaucoma, and uveitis as well as neurological disorders with ocular manifestation. In this review, we describe how microglial function is kept in balance under normal conditions by cross-talk with other retinal cells and summarize how microglia respond to different forms of retinal injury. In addition, we present the concept that microglia play a key role in local regulation of complement in the retina and specify aspects of microglial aging relevant for chronic inflammatory processes in the retina. We conclude that this resident immune cell of the retina cannot be simply regarded as bystander of disease but may instead be a potential therapeutic target to be modulated in the treatment of degenerative and inflammatory diseases of the retina.
authors.affiliation: Laboratory for Experimental Immunology of the Eye, Department of Ophthalmology, University of Cologne, Cologne, Germany.
authors.forename: Marcus
authors.initials: M
authors.lastname: Karlstetter
authors.affiliation: Laboratory for Experimental Immunology of the Eye, Department of Ophthalmology, University of Cologne, Cologne, Germany.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Scholz
authors.affiliation: The John Curtin School of Medical Research, The Australian National University (ANU), Canberra, Australian Capital Territory, Australia.
authors.forename: Matt
authors.initials: M
authors.lastname: Rutar
authors.affiliation: Unit on Neuron-Glia Interactions in Retinal Disease, National Eye Institute, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Wai T
authors.initials: WT
authors.lastname: Wong
authors.affiliation: The John Curtin School of Medical Research, The Australian National University (ANU), Canberra, Australian Capital Territory, Australia.
authors.forename: Jan M
authors.initials: JM
authors.lastname: Provis
authors.affiliation: Laboratory for Experimental Immunology of the Eye, Department of Ophthalmology, University of Cologne, Cologne, Germany. Electronic address: thomas.langmann@uk-koeln.de.
authors.forename: Thomas
authors.initials: T
authors.lastname: Langmann
mesh_terms: D000375:Aging / Q000502:physiology; D000818:Animals; D015415:Biomarkers / Q000032:analysis; D002450:Cell Communication / Q000502:physiology; D003165:Complement System Proteins / Q000502:physiology; D006801:Humans; D007111:Immunity, Cellular / Q000502:physiology; D007249:Inflammation / Q000503:physiopathology; D017628:Microglia / Q000276:immunology / Q000502:physiology*; D012160:Retina / Q000502:physiology*; D012164:Retinal Diseases / Q000175:diagnosis / Q000276:immunology / Q000503:physiopathology*
chemical_list: D015415:Biomarkers; D003165:Complement System Proteins
keywords: Age-related macular degeneration; Aging; Complement system; Diabetic retinopathy; Glaucoma; Neuroinflammation; Retinal dystrophies; Retinal microglia