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Purpose: This study aimed to assess the protective effects of silibinin on blue light-emitting diode (LED)-induced retinal ganglion cells (RGCs) damage. Methods: Silibinin was applied in RGCs damage in vitro model to test its protective effects. Cell viability was assessed with the MTT method and cell apoptosis was evaluated by TUNEL and Annexin V/propidium iodide staining. The expressions of apoptosis related proteins and influenced signalling pathways were measured using western blotting and immunohistochemistry. Inflammatory factors induced by RGC damage were detected using ELISA method. Results: It was found that silibinin in 50 and 100 μM treatment showed a significant protective effect in RGCs under blue light damage. Apoptosis assay showed that silibinin treatment could significantly improve the apoptotic status of RGCs. When the potentially affected signal pathway was considered, blue light would down-regulate the expression of MEK1/ERK/CREB. The levels of inflammatory factors (TNF-α, IL-1β, IL-6 and IL-10) were significantly regulated by silibinin treatment. Conclusions: Silibinin pretreatment would demonstrate protective effect against blue light induced acute RGCs damage. Silibinin treatment has a direct suppression of apoptosis and inflammation through the activation of MEK/ERK/CREB pathway in vitro. [ABSTRACT FROM AUTHOR]