Platinum Nanozymes Counteract Photoreceptor Degeneration and Retina Inflammation in a Light-Damage Model of Age-Related Macular Degeneration

Abstract

Degeneration of photoreceptors in age-related macular degeneration (AMD) is associated with oxidative stress due to the intense aerobic metabolism of rods and cones that if not properly counterbalanced by endogenous antioxidant mechanisms can precipitate photoreceptor degeneration. In spite of being a priority eye disease for its high incidence in the elderly, no effective treatments for AMD exist. While systemic administration of antioxidants has been unsuccessful in slowing down degeneration, locally administered rare-earth nanoparticles were shown to be effective in preventing retinal photo-oxidative damage. However, because of inherent problems of dispersion in biological media, limited antioxidant power, and short lifetimes, these NPs are still confined to the preclinical stage. Here we propose platinum nanoparticles (PtNPs), potent antioxidant nanozymes, as a therapeutic tool for AMD. PtNPs exhibit high catalytic activity at minimal concentrations and protect primary neurons against oxidative insults and the ensuing apoptosis. We tested the efficacy of intravitreally injected PtNPs in preventing or mitigating light damage produced in dark-reared albino Sprague–Dawley rats by in vivo electroretinography (ERG) and ex vivo retina morphology and electrophysiology. We found that both preventive and postlesional treatments with PtNPs increased the amplitude of ERG responses to light stimuli. Ex vivo recordings demonstrated the selective preservation of ON retinal ganglion cell responses to light stimulation in lesioned retinas treated with PtNPs. PtNPs administered after light damage significantly preserved the number of photoreceptors and inhibited the inflammatory response to degeneration, while the preventive treatment had a milder effect. The data indicate that PtNPs can effectively break the vicious cycle linking oxidative stress, degeneration, and inflammation by exerting antioxidant and anti-inflammatory actions. The increased photoreceptor survival and visual performances in degenerated retinas, together with their high biocompatibility, make PtNPs a potential strategy to cure AMD.

Choline Phosphate-Grafted Nanozymes as Universal Extracellular Vesicle Probes for Bladder Cancer Detection

“…All of the nanozymes can oxidize TMB to show a blue color in a few minutes (Figure S4, Supporting Information), confirming that these NPs were peroxidase-mimicking nanozymes. The result further reported that the 5 nm PtNPs show much higher catalytic activity than CeNPs and AuNPs at the same concentration (1 nM) …”

Recent Advances in Nanomedicine for Ocular Fundus Neovascularization Disease Management

“…assessed the effectiveness of intravitreally injected Pt NPs in either preventing or alleviating light‐induced damage in dark‐reared rats and found that both preventive and post‐lesional IVT of Pt NPs led to increased photoreceptors after light damage, further indicating that Pt NPs can effectively disrupt the detrimental cycle that connects oxidative stress, degeneration, and inflammation by acting as both antioxidants and anti‐inflammatory agents. [ 176 ] Intriguingly, for RNV therapies, Xue et al. devised a Pt‐based nanozyme functioned with mitochondria‐targeted ability that can eliminate oxidative damage in RNV (Pt@MitoLipo) (Figure 8b).…”