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Reduced retina microglial activation and improved optic nerve integrity with minocycline treatment in the DBA/2J mouse model of glaucoma.

AbstractPURPOSE:
In the context of the retinal ganglion cell (RGC) axon degeneration in the optic nerve that occurs in glaucoma, microglia become activated, then phagocytic, and redistribute in the optic nerve head. The authors investigated the potential contribution of retinal microglia activation to glaucoma progression in the DBA/2J chronic mouse glaucoma model.
METHODS:
The authors treated 6-week-old DBA/2J mice for 25 weeks with minocycline, a tetracycline derivative known to reduce microglia activation and to improve neuronal survival in other models of neurodegenerative disease. They quantified RGC numbers and characterized microglia activation, gliosis, and both axonal integrity and retrograde tracer transport by RGCs in mice systemically treated with minocycline or vehicle only.
RESULTS:
Minocycline reduced microglial activation and improved RGC axonal transport and integrity, yet it had no effect on the characteristic age-related ocular changes that lead to chronically elevated pressure and did not alter Müller or astrocyte gliosis. Specifically, minocycline increased the fraction of microglia with resting ramified morphology and reduced levels of Iba1 mRNA and protein, a microglia-specific calcium ligand linked to activation. The reduction in microglial activation was coupled to significant improvement in RGC axonal transport, as measured by neuronal retrograde tracing from the superior colliculus. Finally, minocycline treatment significantly decoupled RGC axon loss from increased intraocular pressure.
CONCLUSIONS:
These observations suggest that in glaucoma, retina and optic nerve head microglia activation may be a factor in the early decline in function of the optic nerve and its subsequent degeneration.
AuthorsAlejandra Bosco, Denise M Inman, Michael R Steele, Guangming Wu, Ileana Soto, Nicholas Marsh-Armstrong, Walter C Hubbard, David J Calkins, Philip J Horner, Monica L Vetter
JournalInvestigative ophthalmology & visual science (Invest Ophthalmol Vis Sci) Vol. 49 Issue 4 Pg. 1437-46 (Apr 2008) ISSN: 0146-0404 [Print] United States
PMID18385061 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Chemical References
  • Aif1 protein, mouse
  • Calcium-Binding Proteins
  • Microfilament Proteins
  • Neuroprotective Agents
  • RNA, Messenger
  • Minocycline
Topics
  • Animals
  • Axonal Transport (drug effects)
  • Calcium-Binding Proteins (genetics)
  • Cell Survival
  • Disease Models, Animal
  • Glaucoma (metabolism, pathology, prevention & control)
  • Gliosis (metabolism)
  • Injections, Intraperitoneal
  • Intraocular Pressure
  • Mass Spectrometry
  • Mice
  • Mice, Inbred DBA
  • Microfilament Proteins
  • Microglia (drug effects, metabolism)
  • Minocycline (administration & dosage)
  • Neuroprotective Agents (administration & dosage)
  • Optic Nerve Diseases (metabolism, pathology)
  • RNA, Messenger (metabolism)
  • Retina (cytology)
  • Retinal Ganglion Cells (drug effects, metabolism, pathology)
  • Reverse Transcriptase Polymerase Chain Reaction

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