title: Microglial Activation Promotes Cell Survival in Organotypic Cultures of Postnatal Mouse Retinal Explants.
abstract: The role of microglia during neurodegeneration remains controversial. We investigated whether microglial cells have a neurotoxic or neuroprotective function in the retina. Retinal explants from 10-day-old mice were treated in vitro with minocycline to inhibit microglial activation, with LPS to increase microglial activation, or with liposomes loaded with clodronate (Lip-Clo) to deplete microglial cells. Flow cytometry was used to assess the viability of retinal cells in the explants and the TUNEL method to show the distribution of dead cells. The immunophenotypic and morphological features of microglia and their distribution were analyzed with flow cytometry and immunocytochemistry. Treatment of retinal explants with minocycline reduced microglial activation and simultaneously significantly decreased cell viability and increased the presence of TUNEL-labeled cell profiles. This treatment also prevented the migration of microglial cells towards the outer nuclear layer, where cell death was most abundant. The LPS treatment increased microglial activation but had no effect on cell viability or microglial distribution. Finally, partial microglial removal with Lip-Clo diminished the cell viability in the retinal explants, showing a similar effect to that of minocycline. Hence, cell viability is diminished in retinal explants cultured in vitro when microglial cells are removed or their activation is inhibited, indicating a neurotrophic role for microglia in this system.
authors.affiliation: Departamento de Biología Celular, Facultad de Ciencias, Universidad de Granada, Granada, Spain.
authors.forename: Rosa M
authors.initials: RM
authors.lastname: Ferrer-Martín
authors.affiliation: Departamento de Biología Celular, Facultad de Ciencias, Universidad de Granada, Granada, Spain.
authors.forename: David
authors.initials: D
authors.lastname: Martín-Oliva
authors.affiliation: Departamento de Biología Celular, Facultad de Ciencias, Universidad de Granada, Granada, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Sierra-Martín
authors.affiliation: Departamento de Biología Celular, Facultad de Ciencias, Universidad de Granada, Granada, Spain.
authors.forename: Maria-Carmen
authors.initials: MC
authors.lastname: Carrasco
authors.affiliation: Departamento de Biología Celular, Facultad de Ciencias, Universidad de Granada, Granada, Spain.
authors.forename: María
authors.initials: M
authors.lastname: Martín-Estebané
authors.affiliation: Departamento de Biología Celular, Facultad de Ciencias, Universidad de Granada, Granada, Spain.
authors.forename: Ruth
authors.initials: R
authors.lastname: Calvente
authors.affiliation: Departamento de Biología Celular, Facultad de Ciencias, Universidad de Granada, Granada, Spain.
authors.forename: Sandra M
authors.initials: SM
authors.lastname: Martín-Guerrero
authors.affiliation: Departamento de Biología Celular, Facultad de Ciencias, Universidad de Granada, Granada, Spain.
authors.forename: José L
authors.initials: JL
authors.lastname: Marín-Teva
authors.affiliation: Departamento de Biología Celular, Facultad de Ciencias, Universidad de Granada, Granada, Spain.
authors.forename: Julio
authors.initials: J
authors.lastname: Navascués
authors.affiliation: Departamento de Biología Celular, Facultad de Ciencias, Universidad de Granada, Granada, Spain.
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Cuadros
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002470:Cell Survival; D004002:Clodronic Acid / Q000008:administration & dosage / Q000737:chemistry*; D004926:Escherichia coli; D005434:Flow Cytometry; D007150:Immunohistochemistry; D016130:Immunophenotyping; D008070:Lipopolysaccharides / Q000737:chemistry; D008081:Liposomes / Q000737:chemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000166:cytology*; D008911:Minocycline / Q000737:chemistry; D000066829:Neuroprotection; D009900:Optic Nerve / Q000187:drug effects / Q000254:growth & development*; D009924:Organ Culture Techniques; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D012160:Retina / Q000166:cytology / Q000187:drug effects / Q000254:growth & development*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D008070:Lipopolysaccharides; D008081:Liposomes; D014409:Tumor Necrosis Factor-alpha; D004002:Clodronic Acid; C499321:Parp1 protein, mouse; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases; D008911:Minocycline