Minocycline modulates microglia polarization in ischemia-reperfusion model of retinal degeneration and induces neuroprotection.

Scientific Reports
Amel AhmedChun-Li Zhang

Abstract

Retinal ischemia-reperfusion (IR) injury causes irreversible loss of neurons and ultimately leads to permanent visual impairment and blindness. The cellular response under this pathological retinal condition is less clear. Using genetically modified mice, we systematically examined the behavior of microglia/macrophages after injury. We show that IR leads to activation of microglia/macrophages indicated by migration and proliferation of resident microglia and recruitment of circulating monocytes. IR-induced microglia/macrophages associate with apoptotic retinal neurons. Very interestingly, neuron loss can be mitigated by minocycline treatment. Minocycline induces Il4 expression and M2 polarization of microglia/macrophages. IL4 neutralization dampens minocycline-induced M2 polarization and neuroprotection. Given a well-established safety profile as an antibiotic, our results provide a rationale for using minocycline as a therapeutic agent for treating ischemic retinal degeneration.

References

Jul 1, 1992·Journal of Neurochemistry·P Louzada-JúniorJ Coutinho-Netto
Sep 1, 1993·Medical Hypotheses·D Verma
Mar 1, 1997·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·E N Benveniste
Dec 23, 1998·Proceedings of the National Academy of Sciences of the United States of America·J YrjänheikkiJ Koistinaho
Mar 10, 2001·The Journal of Immunology : Official Journal of the American Association of Immunologists·M HaraK J Wood
Aug 1, 1957·A.M.A. Archives of Ophthalmology·D R LUCAS, J P NEWHOUSE
Feb 10, 2004·Progress in Retinal and Eye Research·Neville N OsborneJosé Melena
Mar 6, 2004·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·David P StirlingWolfram Tetzlaff
Aug 3, 2004·Journal of Neuroinflammation·Wolfgang J StreitW Sue T Griffin
Nov 10, 2004·Eye·N N OsborneJ Melena
Apr 12, 2006·Archives of Ophthalmology·Hani Levkovitch-VerbinShlomo Melamed
Apr 21, 2006·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Bryan C Hains, Stephen G Waxman
Oct 7, 2006·Graefe's Archive for Clinical and Experimental Ophthalmology = Albrecht Von Graefes Archiv Für Klinische Und Experimentelle Ophthalmologie·Nurit MathaloneOrna Geyer
Nov 21, 2007·Nature Neuroscience·Bahareh AjamiFabio M V Rossi
May 14, 2009·The American Journal of Pathology·Sandrine JolyCharlotte E Remé
Oct 30, 2009·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Kristina A KigerlPhillip G Popovich
Dec 19, 2009·The Journal of Comparative Neurology·Ana M SantosMiguel A Cuadros
Apr 9, 2010·Journal of Innate Immunity·Arti PariharAndrea I Doseff
Aug 11, 2010·Archives of Neurology·Jennifer M PlaneWenbin Deng
Sep 3, 2011·Pathology International·Xiaoguang CaoChi-Chao Chan
Dec 4, 2012·Acta Pharmacologica Sinica·Philippe M D'Onofrio, Paulo D Koeberle
Feb 19, 2013·Molecular Nutrition & Food Research·Lei-Lei WangLing Zheng
Feb 28, 2013·British Journal of Pharmacology·N Garrido-MesaJ Gálvez
Mar 9, 2013·Cell Death & Disease·K KobayashiK Kadomatsu
Jun 12, 2013·Experimental Eye Research·Chuan SunYong Tao

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Citations

Jan 24, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Hui ShiXiao-Dong Peng
Jul 3, 2019·International Journal of Molecular Sciences·Hiromitsu KunimiToshihide Kurihara
Mar 2, 2021·Neural Regeneration Research·Gergely SzarkaTamás Kovács-Öller
Mar 16, 2021·Frontiers in Cellular Neuroscience·Juhee KimDong Ho Park
Aug 28, 2021·Journal of Neuroinflammation·Steven F AbcouwerDavid A Antonetti

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Methods Mentioned

BETA
transgenic
confocal microscopy

Software Mentioned

GraphPad Prism
ImageJ
Cell Counter

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