Molybdenum-based antioxidative nanomedicine fighting against retinal pigment epithelium degeneration

Oxidative stress-induced retinal pigment epithelium (RPE) degeneration is the pathologic basis of most retinal degenerative diseases, especially dry age-related macular degeneration (AMD), for which corresponding therapeutic strategies currently were still in their infancy and lack optimal efficacy. In the present study, cerium-doped molybdenum-based polyoxometalate (MoCe) nanoclusters (NCs) are designed as antioxidative nanocatalysts to inhibit oxidative stress-induced RPE degeneration and subsequent retinal damage. The synthesized MoCe NCs display prominent reactive oxygen species (ROS) scavenging efficacy with excellent in vivo biocompatibility. In RPE degeneration mice model, a single intravitreal administration of MoCe NCs effectively inhibit RPE oxidative degeneration and substantially protect retinal structure and visual function. Upon high-throughput sequencing combined with bioinformatics analysis, MoCe administration predominantly restores the expression of DNA repair-related genes and inhibits oxidative stress-induced apoptosis by suppressing the JNK/c-Jun signaling pathway. The ideal biocompatibility and remarkable protective effect render MoCe NCs as the promising nanomedicines combating RPE degeneration-associated retinal diseases especially AMD.