title: [Polysialic Acid for Immunomodulation in an Animal Model for Wet Age-Related Macular Degeneration (AMD)].
abstract: BackgroundChronic activation of the innate immune system is a hallmark of retinal degenerative diseases, including age-related macular degeneration (AMD). Overt microglia and macrophage reactivity, as well as dysregulation of the alternative complement system, trigger and sustain retinal degeneration. It is now accepted that there exists a vicious cycle of mononuclear phagocyte reactivity, abnormal intrinsic complement activation, damage of Bruch's membrane, dysfunction of the retinal pigment epithelium, photoreceptor degeneration and choroidal neovascularization (CNV). Targeting the innate immune system may, therefore, be a complementary approach to anti-angiogenic therapy. This article presents data from polysialic acid treatment experiments in the laser-induced mouse model of wet AMD.Material and MethodsThe laser-CNV mouse model was used to simulate events of neovascular AMD. Polysialic acid was applied by intravitreal injection and microglia activity was assessed with Iba1 staining of retinal and RPE/choroidal flat mounts. Neovascular leakage was determined by fluorescein angiography.ResultsIntravitreal injection of polysialic acid reduced retinal and RPE/choroidal lesion-associated microglia activity in the laser-induced mouse model of AMD. Polysialic acid treatment also diminished vascular leakage at laser spots in this model.ConclusionLocal retinal immunomodulation with polysialic acid presents a novel concept for treatment of inflammatory conditions related to neovascular AMD.
authors.affiliation: Lehrstuhl für Experimentelle Immunologie des Auges, Zentrum für Augenheilkunde, Uniklinik Köln.
authors.forename: Thomas
authors.initials: T
authors.lastname: Langmann
authors.affiliation: Lehrstuhl für Experimentelle Immunologie des Auges, Zentrum für Augenheilkunde, Uniklinik Köln.
authors.forename: Sascha
authors.initials: S
authors.lastname: Fauser
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects / Q000276:immunology*; D056747:Immunomodulation / Q000187:drug effects / Q000276:immunology*; D058449:Intravitreal Injections; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D012160:Retina / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D012794:Sialic Acids / Q000008:administration & dosage* / Q000276:immunology; D016896:Treatment Outcome; D057135:Wet Macular Degeneration / Q000276:immunology* / Q000628:therapy*
chemical_list: D012794:Sialic Acids; C021319:polysialic acid