Abstract
Microbial keratitis (MK) is a major global cause of blindness. Yet, treatment is heavily dependent on antimicrobials with limited options for immunomodulators - despite the critical role of dysregulated immune responses in disease pathogenesis. This gap reflects a critical unmet clinical need and is compounded by the lack of model systems capable of real-time high-resolution immune dynamics analysis. To address this, we developed a zebrafish larvae MK model utilising transgenic zebrafish lines with fluorescently labelled neutrophils, macrophages and basal epithelial cells. Corneal injury triggered rapid immune cell recruitment which was amplified by exposure to pro-inflammatory mediators such as N-formylmethionine-leucyl-phenylalanine (fMLF) and leukotriene B4 (LTB4). Infection with live bacteria induced robust, sustained neutrophil and macrophage recruitment, marked by increased neutrophil speed and migratory distance. This model enables dynamic in vivo visualization of immune cell dynamics, offering a powerful and scalable platform to accelerate the discovery and screening of novel immunomodulators for MK.
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Acknowledgements
The authors would like to acknowledge the University of Edinburgh’s Aquatics Facility staff for fish husbandry assistance, Dr Yi Feng’s group (the University of Edinburgh) for advice and sharing the transgenic lines Tg(K19: EGFP), Tg(LysC: mTurquoise) and Tg(mfap4: tdTomato-CAAX). We acknowledge the support of the Wellcome multi-user equipment grant (WT104915MA). The graphical abstract was created using in BioRender. Cheng, K54. https://BioRender.com/rb4n1c8. This work was supported by Wellcome Trust 320097/Z/24/Z (K.C.). B.M. was supported by the UK Research and Innovation Future Leaders Fellowship MR/V026097/1. A.G.R. was funded by a Medical Research Council (MRC) UK Programme Grant (MR/K013386/1). A.G.R. was also part-funded by an Antimicrobial Resistance UK (AMR) cross-council funding from the MRC to the SHIELD consortium MRNO2995X/1. For the purpose of open access, the author has applied a Creative Commons Attribution (CC BY) licence to any Author Accepted Manuscript version arising from this submission.
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K.C., conceptualisation, data curation, formal analysis, investigation, methodology, writing-original draft, writing-review and editing, visualisation, funding acquisition. C.T., conceptualisation, investigation, methodology, writing-review and editing. J.C.W., investigation, methodology. S.M., investigation, methodology. F.L., investigation, methodology. B.M., conceptualisation, data curation, formal analysis, investigation, methodology, writing-original draft, writing-review and editing. A.G.R., conceptualisation, data curation, formal analysis, investigation, methodology, writing- original draft, writing-review and editing.
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Cheng, K.K.W., Tucker, C.S., Cholewa-Waclaw, J. et al. Real-time characterisation of microbe-induced inflammation using a novel zebrafish larval corneal injury and infection model. Commun Biol (2026). https://doi.org/10.1038/s42003-026-09985-1
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DOI: https://doi.org/10.1038/s42003-026-09985-1
