A conceptual framework and proposed adverse outcome pathway for micro- and nanoplastics accumulation and neurovascular toxicity in the human retina

Micro- and nanoplastics (MNPs) have recently been detected in human retinal tissue, raising concerns about their potential role in neurovascular injury. This paper proposes a conceptual framework and provisional adverse outcome pathway (AOP) to explain how polymer-specific accumulation may contribute to retinal degeneration. Existing empirical findings on retinal plastic burdens were integrated with toxicokinetic principles to construct a polymer-specific model of uptake, retention, and clearance. Mechanistic insights from oxidative stress, inflammation, and barrier dysfunction were synthesized into a stepwise AOP linking molecular initiating events to adverse outcomes. This framework predicts differential retinal retention based on polymer polarity and density: nonpolar, low-density plastics (e.g., polyethylene) tend to clear, whereas polar, dense polymers (e.g., polymethyl methacrylate) accumulate with age. The proposed AOP outlines a cascade from plastic-cell interactions to oxidative stress, inflammation, blood-retinal barrier breakdown, and ultimately neurovascular degeneration. A feedback loop is hypothesized, whereby barrier disruption facilitates further plastic entry. This conceptual model reframes retinal microplastics as active disruptors of homeostasis rather than inert debris. It highlights the retina’s potential as a biosensor for systemic plastic exposure, identifies PMMA as a priority polymer for risk assessment, and suggests therapeutic targets in oxidative stress and barrier protection. Validation through tracer studies, transgenic models, and biomarker development is recommended.