title: Microglia-Müller glia crosstalk in the rd10 mouse model of retinitis pigmentosa.
abstract: Retinitis pigmentosa refers to a large, genetically heterogeneous group of retinal dystrophies. This condition is characterized by the gradual onset of blindness due to progressive deterioration of the retina, a process that includes photoreceptor and retinal-pigmented-epithelium cell decay and death, microglial recruitment, reactive gliosis, and vascular disorganization and regression. We found that early in the degenerative process, the rd10 mouse retina exhibits high levels of photoreceptor cell death and reactive Müller gliosis. In explant cultures, both degenerative processes were abrogated by IGF-I treatment. Moreover, the beneficial effect of IGF-I was diminished by microglial depletion using clodronate-containing liposomes. Interestingly, in the absence of IGF-I, microglial depletion partially prevented cell death without affecting Müller gliosis. These findings strongly suggest a role for microglia-Müller glia crosstalk in neuroprotection. However, a subpopulation of microglial cells appears to promote neurodegeneration in the dystrophic retina. Our findings indicate that beneficial neuroprotective effects may be achieved through strategies that modulate microglial cell responses.
authors.affiliation: 3D Lab (Development, Differentiation and Degeneration), Department of Cellular and Molecular Medicine, Centro de Investigaciones Biológicas, CSIC, C/Ramiro de Maeztu 9, E-28040, Madrid, Spain, anaarroba@gmail.com.
authors.forename: Ana I
authors.initials: AI
authors.lastname: Arroba
authors.forename: Noemí
authors.initials: N
authors.lastname: Alvarez-Lindo
authors.forename: Nico
authors.initials: N
authors.lastname: van Rooijen
authors.forename: Enrique J
authors.initials: EJ
authors.lastname: de la Rosa
mesh_terms: D000818:Animals; D002450:Cell Communication / Q000187:drug effects / Q000502:physiology*; D054707:Cyclic Nucleotide Phosphodiesterases, Type 6 / Q000235:genetics; D004195:Disease Models, Animal; D063928:Ependymoglial Cells / Q000473:pathology*; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017628:Microglia / Q000187:drug effects / Q000473:pathology*; D018696:Neuroprotective Agents / Q000494:pharmacology; D058499:Retinal Dystrophies / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D012174:Retinitis Pigmentosa / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*
chemical_list: D018696:Neuroprotective Agents; D007334:Insulin-Like Growth Factor I; D054707:Cyclic Nucleotide Phosphodiesterases, Type 6; C517438:Pde6b protein, mouse