Protective role of SIRT1 activation against retinal injury caused by polystyrene micro/nanoplastics exposure.

Plastic particles are persistent environmental pollutants that can accumulate in ocular tissues and potentially contribute to retinal damage. Sirtuin 1 (SIRT1), a key regulator of oxidative stress and cellular senescence, may play a protective role against plastic-induced retinal injury, but its role remains unclear. In this study, human retinal pigment epithelial (RPE) cells and rat retinas were directly exposed to polystyrene microplastics (PS-MPs, 2 μm) and nanoplastics (PS-NPs, 50 nm), with and without SIRT activator SRT1720. In vitro analyses included cell viability, intracellular reactive oxygen species (ROS), SIRT1 expression, antioxidant enzyme levels (SOD1, SOD2, CAT), and senescence were assessed. In vivo, rats received intravitreal injections of plastic particles, with or without SRT1720 and oxidative stress-related markers, SIRT1 expression, and senescence were evaluated in retinal tissues 7 days after injection. Results showed that PS-MPs and PS-NPs reduced RPE cell viability in a dose- and time-dependent manner, suppressed SIRT1 and antioxidant enzymes, and increased ROS and senescence. PS-NPs induced stronger ROS and senescence than PS-MPs in vitro. Co-treatment with SRT1720 restored SIRT1 expression, improved antioxidant responses, and attenuated ROS and senescence. In vivo, both particle types induced retinal changes similar to those observed in cell experiments. However, there was no significant toxicity difference between PS-MPs and PS-NPs. In conclusion, PS-MPs or PS-NPs promote oxidative stress and senescence in RPE cells and retinal tissue via downregulation of SIRT1 and antioxidant defenses, while SRT1720 provides protective effects. These findings SIRT1 as a potential therapeutic target for plastic-induced retinal injury.