AbstractPurpose: Rhegmatogenous retinal detachment (RRD) is a sight‐threatening condition with the separation of the neurosensory retina from the retinal pigment epithelium (RPE). Clinical data have associated statin medication with lower risk of re‐vitrectomy in patients operated for RRD. We have previously shown statins to have anti‐inflammatory properties in lipopolysaccharide (LPS)‐treated RPE cells. The purpose of the present study was to examine whether the nonsteroidal anti‐inflammatory drug (NSAID) amfenac could complement the anti‐inflammatory effect of simvastatin in human RPE cells under pathophysiological conditions induced by IL‐1a. In addition to inflammatory markers, we studied the effects of amfenac and simvastatin on growth factors regulating blood vessel formation.Methods: ARPE‐19 cells were pre‐treated with 0.1 μM amfenac and 5 μM simvastatin for 24 h after which 10 pg/ml of IL‐1α was added for 24 h. Enzyme‐linked immunosorbent assay (ELISA) was used to measure secretion of cytokines (IL‐8, MCP‐1), vascular endothelial growth factor (VEGF) and pigment epithelium derived factor (PEDF). Cytotoxicity was measured using the lactate dehydrogenase (LDH) assay.Results: Amfenac and simvastatin were well tolerated upon inflammatory conditions. Both medicines alone and together reduced IL‐1a‐activated IL‐8 release. Simvastatin significantly reduced also the release of MCP‐1. The effect of amfenac alone was not significant but together with simvastatin, significant reduction in MCP‐1 levels was still reached. IL‐1a with the DMSO solvent increased release of PEDF and VEGF compared to DMSO group. Exposure of IL‐1α‐treated cells to amfenac and simvastatin together increased VEGF levels with no changes in the PEDF.Conclusions: Amfenac and simvastatin showed potential to reduce inflammation in the retina upon retinal detachment. Increased VEGF levels may have neuroprotective effects by improving connections between RPE cells and photoreceptors.