title: Reactive retinal microglia, neuronal survival, and the formation of retinal folds and detachments.
abstract: Reactive microglia and macrophages are prevalent in damaged retinas. Accordingly, we investigate how the activation or ablation of microglia/macrophages influences the survival of neurons in the chick retina in vivo. We applied intraocular injections of interleukin 6 (IL6) to stimulate the reactivity of microglia/macrophages and clodronate-liposomes to ablate microglia/macrophages. Activation of the microglia/macrophages with IL6 delays the death of retinal neurons from N-methyl-D-aspartate (NMDA) -induced excitotoxicity. In addition, activation of microglia/macrophages combined with colchicine-mediated retinal damage diminished the survival of ganglion cells. Application of IL6 after an excitotoxic insult greatly exacerbates the damage, and causes widespread retinal detachments and folds, accompanied by accumulation of microglia/macrophages in the subretinal space. Damage-induced retinal folds and detachments were significantly reduced by the ablation of microglia/macrophages. We conclude that microglial reactivity is detrimental to the survival of ganglion cells in colchicine-damaged retinas and detrimental to the survival of photoreceptors in retinal folds. In addition, we conclude that IL6-treatment transiently protects amacrine and bipolar cells against an excitotoxic insult. We propose that suppressing reactivity of microglia/macrophages may be an effective means to lessen the damage and vision loss resulting from damage, in particular during retinal detachment injuries.
authors.affiliation: Department of Neuroscience, College of Medicine, The Ohio State University, Columbus, Ohio.
authors.forename: Andy J
authors.initials: AJ
authors.lastname: Fischer
authors.forename: Christopher
authors.initials: C
authors.lastname: Zelinka
authors.forename: Nima
authors.initials: N
authors.lastname: Milani-Nejad
mesh_terms: D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D016923:Cell Death / Q000187:drug effects; D002645:Chickens; D004002:Clodronic Acid / Q000008:administration & dosage; D004195:Disease Models, Animal; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity; D020287:In Situ Nick-End Labeling; D015850:Interleukin-6 / Q000627:therapeutic use; D017493:Leukocyte Common Antigens; D008081:Liposomes / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects; D017628:Microglia / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D016202:N-Methylaspartate / Q000633:toxicity; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D037121:Plant Lectins; D012160:Retina / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D012163:Retinal Detachment / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology*; D055758:SOX9 Transcription Factor
chemical_list: D018690:Excitatory Amino Acid Agonists; D015850:Interleukin-6; D008081:Liposomes; D037121:Plant Lectins; C017707:Ricinus communis agglutinin-1; D055758:SOX9 Transcription Factor; C527933:Sox9 protein, mouse; D004002:Clodronic Acid; D016202:N-Methylaspartate; D017493:Leukocyte Common Antigens
keywords: Müller glia; microglia; neuronal survival; retina; retinal detachment