Response of Ocular Bacteria Exposure to Cerium Oxide Nanoparticles in Eye Drop Formulation

Cerium oxide nanoparticles (CeO₂ NPs), a few nanometers in diameter, exhibit strong antioxidant and anti-inflammatory activity and are considered promising candidates for the treatment of ocular diseases. This study investigated the impact of CeO₂ NPs, both in their naked form, and formulated as eye drops, on the bacteria inhabiting the ocular surface. The microbiome from healthy eyes was characterized through 16 S rRNA amplicon sequencing. The dominant bacterial genera included Staphylococcus, with lower abundances of Corynebacterium and Streptococcus, varying among the samples. Eye bacteria were isolated and exposed to both forms of CeO₂ NPs to investigate cell growth, viability, and gene expression. Neither naked CeO₂ NPs nor eye drop formulation affected the growth of Staphylococcus aureus and Staphylococcus epidermidis. In S. aureus, CeO₂ caused down-regulation of rho (naked CeO₂ NPs) and recA (eye drop form) genes related to the termination of transcription and DNA damage response, respectively. In S. epidermidis, the expression of lexA, recA, ftsZ, rho and icaC remained comparable between treated and control samples, while DNA damage response genes lexA and recA were up-regulated in C. amycolatum following exposure to CeO₂ eye drops. These gene expression patterns revealed subtle changes in specific bacteria, indicating a short-term adaptive response to eye drop formulations. Overall, these results suggest that CeO₂ NP eye drops have a minimal impact on the isolated bacterial strains. Nonetheless, comprehensive in vivo and clinical studies are necessary to validate these findings, given the inherent limitations of in vitro assays.