High-Fructose High-Fat Diet Renders the Retina More Susceptible to Blue Light Photodamage in Mice

Retinal degeneration is associated with dietary factors and environmental light exposure. This study investigated the effects of a high-fructose high-fat (HFHF) diet on suscepti-bility to blue light (BL)-induced retinal damage. Male ICR mice were randomized into three groups: control, BL, and BL plus HFHF diet (BL + HFHF). The BL + HFHF group consumed the HFHF diet for 40 weeks, followed by 8 weeks of low-intensity BL exposure (465 nm, 37.7 lux, 0.8 μW/cm²) for 6 h daily. The BL group underwent the same BL ex-posure while maintained on a standard diet. Histopathological analysis showed that, under BL exposure, the HFHF diet significantly reduced the number of photoreceptor nuclei and the thickness of the outer nuclear layer and inner/outer segments compared to the BL group (p < 0.05). While BL exposure alone caused oxidative DNA damage, rho-dopsin loss, and Müller cell activation, these detrimental effects were significantly am-plified in the presence of the HFHF diet. Moreover, the HFHF diet increased blood-retinal barrier permeability and triggered apoptotic caspase-3 expression under BL exposure. Mechanistically, the BL + HFHF group exhibited increased retinal advanced glycated end products (AGE) deposition, accompanied by the activation of the receptor for AGE (RAGE), NFκB, and the NLRP3 inflammasome-dependent IL-1β pathway. In conclusion, this study underscores that unhealthy dietary factors, particularly those high in fructose and fat, may intensify the hazard of BL and adversely impact visual health.