Early-Life Exposure to InP/ZnS QDs Triggers Photoreceptor Apoptosis via ER Stress in Zebrafish: Implications for Nanomaterial-Induced Retinal Toxicity.

Quantum dots (QDs) are semiconductor nanoparticles with broad applications across medicine, agriculture, and industry. Our recent work established that indium phosphide/zinc sulfide (InP/ZnS) QDs induced retinal degeneration in zebrafish larvae via uptake by retinal pigment epithelium (RPE). However, the long-term consequences of developmental exposure remain unknown. In this study, we investigated the persistent ocular toxicity in adult zebrafish following early-life (0-72 hpf) InP/ZnS QDs (0, 0.001, 0.01, 0.1 mg/L) exposure. The results showed that early-life exposure to InP/ZnS QDs caused photoreceptor loss and opsin downregulation, accompanied by reduced eye-to-body ratios in adult zebrafish (3 mpf). Mechanistically, TUNEL and immunofluorescence confirmed that InP/ZnS QDs induced endoplasmic reticulum (ER) stress-mediated protein misfolding and photoreceptor apoptosis in 3 mpf zebrafish retinas and a mouse photoreceptor cell line. Moreover, TUDCA, an ER stress inhibitor, partially rescued the reduction in zebrafish ocular axial length and attenuated apoptosis in 661 W cells. In summary, this work identifies InP/ZnS QDs as potent developmental ocular toxicants that trigger ER stress-induced photoreceptor cell apoptosis following early-life exposure, and underscores the urgent need for nanomaterial-specific biosafety guidelines to mitigate delayed-onset visual impairment.