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

ABSTRACT

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.