title: Glaucomatous optic nerve injury involves early astrocyte reactivity and late oligodendrocyte loss.
abstract: Glaucoma, a neurodegenerative disease affecting retinal ganglion cells (RGC), is a leading cause of blindness. Since gliosis is common in neurodegenerative disorders, it is important to describe the changes occurring in various glial populations in glaucoma animal models in relation to axon loss, as only changes that occur early are likely to be useful therapeutic targets. Here, we describe changes occurring in glia within the myelinated portion of the optic nerve (ON) in both DBA/2J mice and in a rat ocular hypertension model. In both glaucoma animal models, we found only a modest loss of oligodendrocytes that occurred after axons had already degenerated. In DBA/2J mice there was proliferation of oligodendrocyte precursor cells (OPCs) and new oligodendrocyte generation. Activation of microglia was detected only in highly degenerated DBA/2J ONs. In contrast, a large increase in astrocyte reactivity occurred early in both animal models. These results are consistent with astrocytes playing a prominent role in regulating axon loss in glaucoma.
authors.affiliation: Hugo W. Moser Research Institute at Kennedy Krieger, Baltimore, Maryland, USA.
authors.forename: Janice L
authors.initials: JL
authors.lastname: Son
authors.forename: Ileana
authors.initials: I
authors.lastname: Soto
authors.forename: Ericka
authors.initials: E
authors.lastname: Oglesby
authors.forename: Teresa
authors.initials: T
authors.lastname: Lopez-Roca
authors.forename: Mary E
authors.initials: ME
authors.lastname: Pease
authors.forename: Harry A
authors.initials: HA
authors.lastname: Quigley
authors.forename: Nicholas
authors.initials: N
authors.lastname: Marsh-Armstrong
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000473:pathology / Q000502:physiology; D001369:Axons / Q000473:pathology / Q000502:physiology; D049109:Cell Proliferation; D004195:Disease Models, Animal; D005901:Glaucoma / Q000473:pathology / Q000503:physiopathology*; D005911:Gliosis / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D017628:Microglia / Q000473:pathology / Q000502:physiology; D009186:Myelin Sheath / Q000473:pathology / Q000502:physiology; D009457:Neuroglia / Q000473:pathology / Q000502:physiology*; D009836:Oligodendroglia / Q000473:pathology / Q000502:physiology; D009900:Optic Nerve / Q000473:pathology / Q000503:physiopathology*; D009901:Optic Nerve Diseases / Q000473:pathology / Q000503:physiopathology*; D051381:Rats; D017208:Rats, Wistar; D012165:Retinal Ganglion Cells / Q000473:pathology / Q000502:physiology; D013234:Stem Cells / Q000473:pathology / Q000502:physiology; D013997:Time Factors; D014855:Wallerian Degeneration / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*