Biomaterials. 2026 Jan 17;330:124007. doi: 10.1016/j.biomaterials.2026.124007. Online ahead of print.
ABSTRACT
Retinal ischemia-reperfusion injury (RIRI) is a central pathological mechanism in vision-impairing disorders such as glaucoma and retinal vascular occlusion. Current treatment modalities are significantly constrained by their inability to simultaneously address the multifaceted injury cascades driven by lethal oxidative stress, ferroptosis, and neuroinflammation, which considerably limits their clinical efficacy. To overcome these challenges, we designed a nanocomposite, termed P-PPy, by integrating polydopamine with conducting polypyrrole. Within this construct, surface-modified polydopamine (PDA) acts as a biosponge that effectively chelates excess iron ions. A single intravitreal injection of P-PPy elicited broad therapeutic responses, including efficient reactive oxygen species (ROS) scavenging, inhibition of ferroptosis in retinal ganglion cells accompanied by restoration of mitochondrial functionality, and induction of M2 microglial polarization leading to attenuated neuroinflammation. Together, these mechanisms synergistically restored the electrophysiological microenvironment of the retina, markedly preserving both its structural integrity and functional performance. The P-PPy nanocomposite also demonstrated an excellent biosafety profile, exhibiting no detectable toxicity in both cellular assays and following intravitreal administration in animal models. In summary, this readily synthesizable, multifunctional conductive nanoplatform provides strong neuroprotective effects in vivo, offering a promising therapeutic avenue based on conductive nanomaterials for the treatment of neurodegenerative retinal diseases.
PMID:41576480 | DOI:10.1016/j.biomaterials.2026.124007