An endoplasmic reticulum-targeted NIR fluorescent nanoprobe for early diagnosis of glaucoma in vivo

Glaucoma is a leading cause of irreversible blindness worldwide and characterized by progressive loss of retinal ganglion cells (RGCs). As glaucoma progresses asymptomatically and the lack of specific biomarkers or noninvasive imaging tools during the early stage, it is often discovered at a relatively late stage without cure. Development of an effective tool for early diagnosis remains a necessity. As well known, endoplasmic reticulum (ER) stress and subsequent accumulation of reactive oxygen species (ROS) play a vital role in the development of glaucoma, with peroxynitrite (ONOO- ) as one of the most abundant cytotoxic ROS. In this work, we constructed a novel near-infrared (NIR) fluorescent nanoprobe named ER-ONOO-NPs. It specifically and sensitively targets ER-associated ONOO- with low biotoxicity in cultured RGCs. Systematically applied to the NMDA-induced mouse model of glaucoma, ER-ONOO-NPs performs well for real-time dynamic monitoring of ONOO- fluctuations at the Ganglion cell layer of mice prior to RGCs apoptosis. Thus, our results suggest that the ER-targeted NIR fluorescent nanoprobe could be a noninvasive imaging tool for early diagnosis of glaucoma in high-risk population.