Morphology-associated ocular surface toxicity of micro- and nanoplastics: Fiber embedding contributes to persistent injury.

Micro- and nanoplastics (MNPs) are ubiquitous contaminants, yet how particle shape modulates ocular surface toxicity remains unclear. Here, we compared two red-fluorescent polystyrene spherical MNP preparations with nominal diameters of 80 nm and 200 nm, respectively, with red-fluorescent polyacrylonitrile Fiber MNPs (approximately 200 nm in diameter and 2-3 μm in length) to define their effects on the corneal epithelium and ocular surface functional unit. In vitro, all MNP types were internalized by human corneal epithelial (HCE-T) cells with perinuclear accumulation and induced dose- and time-dependent cytotoxicity, including reduced viability, increased ROS, elevated TUNEL positivity, ZO-1 downregulation, and impaired epithelial migration; notably, 80 nm PS MNPs elicited stronger early toxicity. In vivo, chronic topical exposure produced corneal epithelial damage, tear-film instability, conjunctival goblet-cell depletion, reduced corneal nerve density, and lacrimal gland inflammatory activation. Live imaging and scanning electron microscopy confirmed deposition, with Fiber MNPs showing surface embedding and disruption of corneal epithelial microvillar microarchitecture. Transcriptomic profiling with in vitro/in vivo validation showed enrichment of MAPK signaling and activation-associated changes in the MAP3K8-ERK/JNK/p38 axis, accompanied by a sustained pro-inflammatory transcriptional program, with more persistent inflammatory signaling in the Fiber MNP group. Together, these findings demonstrate particle type- and morphology-associated ocular surface toxicity of MNPs and support considering particle morphology together with polymer identity, size, and particle number in future ocular health risk assessment.