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Icariin was reported to be a safe and effective natural anti\u2010inflammatory drug. Herein, we evaluated the long\u2010term therapeutic effects of a single intravitreal injection of poly(lactide\u2010co\u2010glycolide) PLGA\u2013icariin in a rat model of anterior ischemic optic neuropathy (rAION). Treatment with PLGA microspheres of icariin preserved the visual function and RGC density for 1\u2009month in the rAION model. In addition, ON edema and macrophage infiltration were inhibited by treating PLGA microspheres of icariin. We found that the binding complex of icariin and CCAAT enhancer binding protein beta (CEBP\u2010\u03b2) significantly induced endogenous granulocyte colony\u2010stimulating factor (G\u2010CSF) expression to activate noncanonical nuclear factor kappa B (NF\u2010\u03baB) signaling pathway by promoting an alternative phosphorylation reaction of IKK\u2010\u03b2. Activation of noncanonical NF\u2010\u03baB signaling pathway promoted the M2 microglia\/macrophage polarization and AKT1 activation, which prevented neuroinflammation and RGC apoptosis after ON infarct. This study concluded that protective mechanism of icariin is a CEBP\u2010\u03b2\/G\u2010CSF axis\u2010induced noncanonical NF\u2010\u03baB activation, which provides the long\u2010term neuroprotective effects via anti\u2010inflammatory and antiapoptotic actions after ON ischemia.<\/jats:p>","DOI":"10.1002\/btm2.10289","type":"journal-article","created":{"date-parts":[[2021,12,28]],"date-time":"2021-12-28T23:16:08Z","timestamp":1640733368000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Long term therapeutic effects of icariin\u2010loaded\n                    <scp>PLGA<\/scp>\n                    microspheres in an experimental model of optic nerve ischemia via modulation of\n                    <scp>CEBP<\/scp>\n                    \u2010\u03b2\/\n                    <scp>G\u2010CSF<\/scp>\n                    \/noncanonical\n                    <scp>NF\u2010<\/scp>\n                    \u03ba\n                    <scp>B<\/scp>\n                    axis"],"prefix":"10.1002","volume":"7","author":[{"given":"Tushar Dnyaneshwar","family":"Desai","sequence":"first","affiliation":[{"name":"Institute of Eye Research Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation  Hualien Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yao\u2010Tseng","family":"Wen","sequence":"additional","affiliation":[{"name":"Institute of Eye Research Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation  Hualien Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jayasimha Rayalu","family":"Daddam","sequence":"additional","affiliation":[{"name":"Department of Animal Science Agriculture Research Organization, Volcani Center  Rishon LeTsiyon Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felice","family":"Cheng","sequence":"additional","affiliation":[{"name":"Drug Delivery Technology Department Industrial Technology Research Institute  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