Docosahexaenoic acid aggravates photooxidative damage in retinal pigment epithelial cells via lipid peroxidation

• DHA can promote the proliferation of RPE cells under dark conditions.
• DHA should be a molecular target of photo-oxidative stress for RPE cells.
• DHA aggravates photo-oxidative damage in RPE cells via lipid peroxidation.
• DHA has dual functions in retinal physiology and pathology.

Docosahexaenoic acid (DHA, 22:6n-3), a long-chain polyunsaturated fatty acid (PUFA) with important functions in normal human retinal activity and vision development, is recommended to promote brain and eye development. However, recent research has revealed that increased DHA level in the retina due to linoleic acid-rich diet heightens the vulnerability of the retina to photooxidative stress. Thus, many scholars have analyzed the potential risks of DHA intake on retinal damage. This study evaluated the potential adverse effects of DHA intake on individuals usually exposed to high-light intensity conditions using a visible light-induced retinal pigment epithelium (RPE) cell damage model in vitro. Results showed that DHA promoted the proliferation of RPE cells without any cytotoxicity under dark conditions. However, DHA supplement elicited deleterious effects on RPE cells under high-intensity light conditions. That is, DHA supplement inhibited cellular proliferation, destroyed cell membrane integrity, enhanced cellular senescence, increased vascular endothelial growth factor (VEGF) release, and decreased phagocytic function. Moreover, DHA supplement increased the intracellular and extracellular levels of reactive oxygen species and the extracellular level of lipid peroxidation products under high-intensity light conditions. These results demonstrate that DHA increases the vulnerability of the retina to light damage through lipid peroxidation.