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<span class="s18"><span class="bumpedFont20"><strong>Background and objectives:</strong> </span></span><span class="s19"><span class="bumpedFont20">Crocus sativus</span></span><span class="s4"><span class="bumpedFont20"> L. (Iridaceae) commonly known as saffron, is a popular spice which is used for its pleasant aroma and favored color. Regarding the previous reports about the neuroprotective behavior of saffron or its constituents, in the present work, the neuroprotective property of saffron in rat retina was investigated against light damage in a system biology study. </span></span><strong><span class="s18"><span class="bumpedFont20">Methods:</span></span></strong><span class="s4"><span class="bumpedFont20"><strong> </strong>Retina gene profiles of 4 groups (each group including 3 samples) </span></span><span class="s4"><span class="bumpedFont20">o</span></span><span class="s4"><span class="bumpedFont20">f rats (control; C light damage; L, Saffron; S, and saffron-light damage; SL) which are included in GSE22818 were extracted from Gene Expression Omnibus (GEO).  The significant differentially expressed genes (DEGs) from C-L groups analysis which are not included in S-SL comparison were screened by pathway analysis to find the critical protected genes against light damage by saffron. </span></span><span class="s18"><span class="bumpedFont20"><strong>Results:</strong> </span></span><span class="s4"><span class="bumpedFont20">Numbers of 46 gene were protected by saffron versus light damage significantly. The findings revealed that Casp3, Myd88, Birc3, Tnfrsf1a, </span></span><span class="s4"><span class="bumpedFont20">Myc</span></span><span class="s4"><span class="bumpedFont20">, Nfkb2, Fgf2 were the important protected genes by saffron against light damage. “MAPK signaling pathway” and “apoptosis” were highlighted as important related pathways for 46 DEGs. </span></span><span class="s18"><span class="bumpedFont20"><strong>Conclusion:</strong> </span></span><span class="s4"><span class="bumpedFont20">Saffron protects a part of light damage which is controlled mostly by Casp3, Myd88, Birc3, Tnfrsf1a, </span></span><span class="s4"><span class="bumpedFont20">Myc</span></span><span class="s4"><span class="bumpedFont20">, Nfkb2, Fgf2. It seems other parts of damage should be studied in more details to find a complete prospective of molecular mechanism of light damage effect on retina.  </span></span>