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

Alejandra 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

Research output: Contribution to journalArticle

179 Citations (Scopus)

Abstract

Purpose. 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 Muller or astrocyte gliosis. Specifically, minocycline increased the fraction of microglia with resting ramified morphology and reduced levels of Iba1 mRNA and protein, a microglia-spe-cific 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.

Original languageEnglish (US)
Pages (from-to)1437-1446
Number of pages10
JournalInvestigative Ophthalmology and Visual Science
Volume49
Issue number4
DOIs
StatePublished - Apr 1 2008
Externally publishedYes

Fingerprint

Inbred DBA Mouse
Minocycline
Microglia
Optic Nerve
Glaucoma
Retina
Retinal Ganglion Cells
Axonal Transport
Gliosis
Optic Disk
Axons
Superior Colliculi
Tetracycline
Intraocular Pressure
Astrocytes
Neurodegenerative Diseases
Cell Count
Ligands
Calcium
Pressure

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

Cite this

Reduced retina microglial activation and improved optic nerve integrity with minocycline treatment in the DBA/2J mouse model of glaucoma. / Bosco, Alejandra; Inman, Denise M.; Steele, Michael R.; Wu, Guangming; Soto, Ileana; Marsh-Armstrong, Nicholas; Hubbard, Walter C.; Calkins, David J.; Horner, Philip J.; Vetter, Monica L.

In: Investigative Ophthalmology and Visual Science, Vol. 49, No. 4, 01.04.2008, p. 1437-1446.

Research output: Contribution to journalArticle

Bosco, Alejandra ; Inman, Denise M. ; Steele, Michael R. ; Wu, Guangming ; Soto, Ileana ; Marsh-Armstrong, Nicholas ; Hubbard, Walter C. ; Calkins, David J. ; Horner, Philip J. ; Vetter, Monica L. / Reduced retina microglial activation and improved optic nerve integrity with minocycline treatment in the DBA/2J mouse model of glaucoma. In: Investigative Ophthalmology and Visual Science. 2008 ; Vol. 49, No. 4. pp. 1437-1446.
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AU - Bosco, Alejandra

AU - Inman, Denise M.

AU - Steele, Michael R.

AU - Wu, Guangming

AU - Soto, Ileana

AU - Marsh-Armstrong, Nicholas

AU - Hubbard, Walter C.

AU - Calkins, David J.

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AU - Vetter, Monica L.

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