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We have previously demonstrated that the activation of M\u00fcller cells and gliosis in the degenerative retina are significantly suppressed by the subretinal transplantation of a mixture of olfactory ensheathing cells (OECs) and olfactory nerve fibroblasts. However, the underlying molecular mechanism has remained elusive. Here we transplanted purified rat OECs into the subretinal space of pigmented Royal College of Surgeons (RCS) rats, a classic rodent model of retinal degeneration. Using behavioral testing and electroretinography, we confirmed that the grafted OECs preserved the visual function of rats for 8 weeks, relative to vehicle controls (phosphate-buffered saline). Histological evaluation of outer nuclear layer thickness and composition demonstrated that more photoreceptors and ON-bipolar cells were preserved in the retinas of OEC-treated RCS rats than in controls. The grafted OECs migrated into the outer plexiform layer, inner nuclear layer, and inner plexiform layer. They interacted directly with M\u00fcller cells in the retina of RCS rats, in three distinct patterns, and secreted matrix metalloproteinases 2 and 3. Previous studies have demonstrated that rat OECs express delta-like ligand (DLL), while M\u00fcller cells express Notch3, the receptor for DLL. Here we found that the grafted OECs significantly decreased the expression, by retinal cells, of Notch signaling pathway components (including Notch3, Notch4, DLL1, DLL4, Jagged1, Hes1, and Hes5) 2 weeks after the cell transplantation and that this effect persisted for a further 2 weeks. Based on these findings, we suggest that transplanted OECs inhibit the activation of M\u00fcller cells and the associated gliosis, at least partly through suppression of the Notch pathway.<\/jats:p>","DOI":"10.3727\/096368917x694994","type":"journal-article","created":{"date-parts":[[2017,2,10]],"date-time":"2017-02-10T06:05:20Z","timestamp":1486706720000},"page":"967-982","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":17,"title":["Olfactory Ensheathing Cells Inhibit Gliosis in Retinal Degeneration by Downregulation of the M\u00fcller Cell Notch Signaling Pathway"],"prefix":"10.1177","volume":"26","author":[{"given":"Jing","family":"Xie","sequence":"first","affiliation":[{"name":"Southwest Hospital\/Southwest Eye Hospital, Third Military Medical University, Chongqing, P.R. China"},{"name":"Key Lab of Visual Damage, Regeneration and Restoration of Chongqing, Chongqing, P.R. 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