Melanin Nanoparticles as an Alternative to Natural Melanin in Retinal Pigment Epithelium Cells and Their Therapeutic Effects against Age-Related Macular Degeneration

Melanin is a natural pigment that is widely distributed in many parts of the human body, such as the skin and retinal pigment epithelium (RPE) in eyes. In contrast to skin melanin, which is being constantly synthesized by the epidermal melanocytes, melanin in the RPE does not regenerate. Melanin is known to function as a potential radical scavenger and photoprotective agent. However, the protective effects of melanin against oxidative stress decline with increasing age. This phenomenon has been significantly correlated with the pathogenesis of age-related macular degeneration (AMD). To increase the potential antioxidant and photoprotective characteristics of the melanin, we designed a new strategy by replenishment of melanin using PEGylated-synthetic melanin nanoparticles (MNPs) in the RPE for the treatment of AMD. We performed experiments using AMD-like cellular and mouse models and demonstrated that MNPs are safe, biocompatible, and selectively target reactive oxygen species (ROS) with powerful antioxidant properties. MNPs can traffic and accumulate in the RPE and are exclusively located in cytosol, but not the nucleus and mitochondria of the cells, for up to three months after a single-dose intravitreal (IVT) injection. Our findings demonstrate, for the first time, that MNPs are able to substitute for natural melanin in the RPE of eyes and suggest the potential efficacy of MNPs as a natural radical scavenger against oxidative stress in ROS-related diseases, such as AMD. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=88 SRC="FIGDIR/small/481315v2_ufig1.gif" ALT="Figure 1"> View larger version (26K): org.highwire.dtl.DTLVardef@18929e6org.highwire.dtl.DTLVardef@1dc929org.highwire.dtl.DTLVardef@181c8c2org.highwire.dtl.DTLVardef@1a36eab_HPS_FORMAT_FIGEXP M_FIG C_FIG Intracellular trafficking showing that PEGylated-synthetic melanin nanoparticles (MNPs) reach their target and are stable in the retinal pigment epithelial cells for up to 3 months via a single-dose intravitreal (IVT) injection.