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This study aimed to investigate whether use of a selective-blue-filtering (S-BF) lens can protect cultured primary porcine RPE cells against photo-irradiation. Transmittance of S-BF and UV-filtering (UVF) lenses was characterised spectrophotometrically. RPE cells were exposed to 1700 lux of white (peak λ at 443 and 533 nm; 0.44 mW/cm2) or blue (peak λ at 448 and 523 nm; 0.85 mW/cm2) LED light for 16 h to evaluate the influence of light source on the culture. The effect of the S-BF and UVF ophthalmic lenses on RPE cell cultures under blue light irradiation was then investigated. Cell viability was compared using trypan blue and MTT assays. Intracellular ROS production was detected by a fluorescein probe CM-H2DCFDA. Expression levels of catalase and Prdx3 were analysed by western blot. Trypan blue staining showed blue light caused more cell death than no light (p = 0.001) or white light (p = 0.005). MTT assay supported the hypothesis that exposure to blue light damaged RPE cells more severely than no light (p = 0.002) or white light (p = 0.014). Under blue light, use of the S-BF lens, which blocked 17% more blue light than the UVF lens, resulted in higher cellular viability (S-BF: 93.4±1.4% vs UVF: 90.6±1.4%; p = 0.022; MTT: 1.2-fold; p = 0.029). Blue and white light both significantly increased ROS production. The S-BF lens protected cells, resulting in lower levels of ROS and higher expression of catalase and Prdx3. To conclude, blue LED light exposure resulted in significant cytotoxicity to RPE cells. Partial blockage of blue light by an S-BF lens led to protective effects against retinal phototoxicity, which were mediated by reduction of ROS and increased levels of antioxidant enzymes. [ABSTRACT FROM AUTHOR]