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Nitric Oxide-Releasing Nanoparticles for Retinal Protection Against Blue Light-Induced Oxidative and Vascular Injury
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DOI：10.1021/acsanm.6c02509.png)
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Abstract
En 中文
Excessive exposure to blue light (BL) contributes to oxidative stress, vascular dysfunction, and progressive retinal degeneration. Nitric oxide (NO), a vasoprotective and antioxidant signaling molecule, holds therapeutic promise but is limited by poor stability and short half-life in biological environments. Here, we report an organosilica nanoparticle-based, NO-releasing system (NORS) designed for localized, sustained, and light-responsive NO delivery to the retina. NORS nanoparticles were synthesized via a direct precursor-to-nanoparticle route using a thiol–organosilane precursor, in which S-nitrosation and silica condensation proceeded concurrently under one-pot aqueous conditions. The resulting colloids (hydrodynamic diameter ≈130 nm, zeta potential ≈−10 mV) exhibited stable dispersion and continuous basal NO release for up to 72 h, with light-triggered NO flux precisely tunable according to BL intensity. In vitro experiments were conducted in human retinal pigment epithelial cells (ARPE-19) to evaluate the cytocompatibility, intracellular uptake, and antioxidant response of NORS under BL exposure. The assays included assessments of cell viability, reactive oxygen species generation, and activation of redox signaling pathways following treatment with NORS in the presence or absence of BL irradiation. In vivo efficacy was evaluated in C57BL/6 mice subjected to chronic BL exposure (300 lx, 12 h/day for 28 days). Topical administration of NORS at an S-nitrosothiol-equivalent concentration of 1 μM was performed daily to assess ocular biocompatibility and retinal protection. Retinal vascular permeability, perfusion, and structural integrity were examined by fundus fluorescein angiography, laser speckle flowgraphy, optical coherence tomography, and histological analysis. Functional recovery was assessed by electroretinography. NORS effectively reduced BL-induced vascular leakage and perfusion deficits, preserved photoreceptor electrophysiological responses, and maintained retinal morphology without causing ocular irritation or toxicity. Collectively, the NORS nanoparticles provide a sustained and tunable NO-delivery platform that mitigates BL-induced oxidative and vascular stress. This material-based approach offers a promising strategy for redox modulation and retinal protection.
Keywords:
Nanoparticles
Oxidative stress
Oxides
Peptides and proteins
Stress
nitric oxide
ophthalmic delivery
blue light
retinal oxidative stress
vascular dysfunction
nanocarrier
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