Targeting oxidative stress and inflammation in retinal degeneration with Platinum Nanozymes

The various forms of neurodegeneration stem from a damaging interplay of oxidative stress, neuronal death, and inflammation, which create a pathological cycle responsible for pathological progression. Conditions like retinitis pigmentosa (RP) and age-related macular degeneration (AMD) are linked to these mechanisms in the eye. This study suggests using platinum nanoparticles (PtNPs) that act like antioxidant enzymes, such as catalase and superoxide dismutase, to disrupt this harmful cycle. Thanks to their small size, reactive surface, and high biocompatibility, PtNPs exhibit high catalytic activity even at minimal concentrations and show stability to changes in temperature and pH within biological environments, resulting in long-lasting effects. In this work, we tested the efficacy of this approach by intravitreally injecting PtNPs into two animal models: Sprague Dawley Light-Damage (LD) rats and Royal College of Surgeons (RCS) rats. These models recapitulate the main features of age-related macular degeneration (AMD) and retinitis pigmentosa (RP), respectively. In the LD model, we applied two approaches, differing in the timing of PtNPs administration, aiming to prevent and cure the effects of acute or chronic photooxidative damage. Visual function was evaluated in vivo using electroretinograms (ERG) and ex vivo on explanted retinas by recording light-driven responses from thousands of retinal ganglion cells (RGCs) with a high-density MEA. We also assessed photoreceptor survival, and the inflammatory response mediated by microglia and macroglia. ERG analysis shows that PtNPs injections preserve the a-wave (photoreceptors), and b-wave (second-order neurons) amplitudes compared to sham-injected animals in preventive and curative protocols. At the same time, HD-MEA technology revealed that ON RGCs were significantly preserved compared to control animals. Moreover, in the LD model, PtNPs injections resulted in a preserved photoreceptor layer and reduced inflammation, especially in the curative protocol. Abstract ii In RCS rats, PtNPs administration at an early stage (p30) of degeneration led to significant rescue in visual behaviour, as measured by the light/dark box test and the fear conditioning test, along with substantial preservation of the photoreceptor layer. These findings highlight the potential of PtNPs to break the oxidative stress and inflammation cycle, positioning them as a promising treatment for a spectrum of retinal degenerative diseases. Notably, since this pathological cycle is typical of various neurodegenerative conditions, PtNPs could have universal applicability as a treatment across multiple neurodegenerative diseases.