Purchase this article with an account.
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)
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.
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.
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.
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.
This PDF is available to Subscribers Only