April 2010
Volume 51, Issue 13
ARVO Annual Meeting Abstract  |   April 2010
Assessing Microglia/Macrophages in DBA/2J Glaucoma
Author Affiliations & Notes
  • G. R. Howell
    Howard Hughes Med Institute,, Bar Harbor, Maine
  • X. Zhu
    Howard Hughes Med Institute,, Bar Harbor, Maine
  • L. Van Eldik
    Northwestern University Feinberg School of Medicine, Chicago, Illinois
  • M. Watterson
    Northwestern University Feinberg School of Medicine, Chicago, Illinois
  • S. W. M. John
    Howard Hughes Med Institute,, Bar Harbor, Maine
  • Footnotes
    Commercial Relationships  G.R. Howell, None; X. Zhu, None; L. Van Eldik, None; M. Watterson, None; S.W.M. John, None.
  • Footnotes
    Support  Howard Hughes Medical Institute, XZ was supported by a grant from The Glaucoma Foundation
Investigative Ophthalmology & Visual Science April 2010, Vol.51, 2098. doi:
  • Views
  • Share
  • Tools
    • Alerts
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      G. R. Howell, X. Zhu, L. Van Eldik, M. Watterson, S. W. M. John; Assessing Microglia/Macrophages in DBA/2J Glaucoma. Invest. Ophthalmol. Vis. Sci. 2010;51(13):2098.

      Download citation file:

      © ARVO (1962-2015); The Authors (2016-present)

  • Supplements

Purpose: : Glaucoma is an age-related neurodegenerative disorder characterized by the death of retinal ganglion cells (RGCs). Previous reports suggest microglia/macrophages participate in glaucoma. Gene expression studies of DBA/2J (D2) mice show that microglia/macrophage-relevant genes are upregulated during early stages of glaucoma. However, the precise role of microglia/macrophages in glaucoma remains unclear.

Methods: : We assessed microglia/macrophages in D2, D2.Cx3cr1-GFP (express GFP in microglia/macrophages) and D2-Gpnmb+ control mice at a variety of ages and severity of glaucoma. We have used immunofluorescence with antibodies for AIF1 (IBA1, all microglia/macrophages) and CD68 (activated microglia/macrophages). In initial experiments to functionally assess the importance of microglia/macrophage activation, we have separately administered Minozac and Minocycline. These two compounds target proinflammatory responses in microglia. Compounds were administered to D2 mice at 7.5 months of age, just prior to when significant IOP elevation is first observed in D2 mice. Optic nerve damage and RGC loss was assessed at 2 key glaucoma ages.

Results: : Activated microglia/macrophage numbers increase in the ONH and retina prior to significant RGC loss. In particular, significant numbers of activated microglia are observed in the optic nerve at the junction where myelination begins. Minozac significantly decreased the severity of glaucoma whereas Minocycline significantly increased the severity. These differences may be due to the different modes of action for Minozac and Minocycline. Minozac specifically targets proinflammatory responses, whereas Minocycline targets a range of additional processes.

Conclusions: : Targeting proinflammatory responses with Minozac can significantly reduce glaucoma in D2 mice. However, microglia and macrophages are likely to play multiple roles during different stages of glaucoma, some protective and some damaging. This is an important consideration when developing neuroprotective therapies for human glaucoma.

Keywords: microglia • neuroprotection 

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.