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

被引:53
作者
Ahmed, Amel [1 ,3 ]
Wang, Lei-Lei [1 ,2 ]
Abdelmaksoud, Safaa [3 ]
Aboelgheit, Amal [3 ]
Saeed, Safaa [3 ]
Zhang, Chun-Li [1 ,2 ]
机构
[1] Univ Texas Southwestern Med Ctr Dallas, Dept Mol Biol, Dallas, TX 75390 USA
[2] Univ Texas Southwestern Med Ctr Dallas, Hamon Ctr Regenerat Sci & Med, Dallas, TX 75390 USA
[3] Assiut Univ, Dept Histol & Cell Biol, Fac Med, Assiut, Egypt
关键词
FATE MAPPING REVEALS; OPTIC-NERVE; MOUSE MODEL; INTRAVITREAL INJECTION; FREE-RADICALS; RAT MODEL; ACTIVATION; MACROPHAGES; CELLS; EXPRESSION;
D O I
10.1038/s41598-017-14450-5
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
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页数:16
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