Abstract
Purpose :
Excessive oxidative stress leads to nonspecific inflammation and is a major cause of pathogenesis of both wet and dry forms of age-related macular degeneration (AMD). Melanin is naturally present in pigmented tissues, such as the retinal pigment epithelium (RPE) in eyes, and has a strong ability to scavenge a broad range of free radicals. By combining melanin with nanoceria to take advantage of nanoceria’s auto-regenerative antioxidant property, we have developed a novel nanoceria-coated melanin antioxidant (CCM) which can potentially achieve long-term effects through a single-dose administration and relieve pathological damages for AMD.
Methods :
We introduced ceria nanoparticle on the melanin matrix for its auto-regenerative activity and demonstrated the size, shape, charge, and elemental composition through analytic methods, including TEM, DLS, and EDS. We investigated antioxidant and free radical scavenging by using DPPH, Evans blue bleaching, and Amplex red assays. Furthermore, we evaluated the cell cytotoxicity and antioxidative properties of melanin and CCM in vitro using a H2O2-induced oxidative stress in mouse primary RPE cells (mRPE) through various biological experimental techniques.
Results :
Melanin and CCM were characterized by different physicochemical techniques. The TEM of melanin was shown uniform nanospheres with an average diameter of ~100 nm. Cerium ions were effectively chelated with catechol groups in melanin matrices and grown to cerium oxide (~5 nm scale), which was clearly shown on the surface of melanin matrix through elemental mapping images. Notably, CCM was explored as highly water stable over 9 months (last time checked) at room temperature. Compared with melanin, CCM showed enhanced antioxidant activities with auto-regenerative properties against the deleterious effects of a broad range of reactive oxygen and nitrogen species (RONS). Furthermore, the cell viability toward the mRPE cells was above 80 % after 48 hours exposure of melanin or CCM, indicating that they are safe and well tolerated.
Conclusions :
CCM can protect mRPE cells not only from chemically induced oxidative stress by scavenging a broad range of RONS molecules, but also has the ability to continually scavenge free radicals, owing to the added auto-regenerative property. The newly developed CCM is biocompatible and can be used as a robust antioxidant to attenuate pathological damages in AMD.
This is a 2021 ARVO Annual Meeting abstract.