Corneal Injury and Repair in the Zebrafish

Suboptimal repair following trauma or corrective surgery can result in permanent visual impairment. We developed a new ocular injury model using wild‐type and transgenic zebrafish, in order to study the cellular and molecular mechanisms of the corneal repair response. Using light, transmission and scanning electron microscopy, we demonstrate that the thermal ablation of the fish central corneal region results in the epithelium loss, collagen fiber disintegration and keratocytes necrosis in the corneal stroma. Response to this injury consisted first of a robust influx of heterophils in the wound border of the tg(MPX‐GFP) transgenic zebrafish. Wound closure was achieved by 24 hours with a multilayered and adematous epithelium displaying loose intercellular contacts. Stromal and epithelial inflammation persisted several days beyond wound closure. Interestingly in the initial wound periphery, heterophils were found migrating between the orthogonally oriented bundle of collagen, and in apposition to the stromal keratocytes, suggesting heterophil‐keratocyte adhesive contacts may provide directional cues for inflammatory cells migration. The gross restoration of corneal tissue structure, the return of keratocytes, and the re‐patterning of stromal collagen approaching that of uninjured cornea was observed by day 7. Our study reveals that a dynamic and complex injury response program is orchestrated in the zebrafish cornea upon injury. We demonstrate that the zebrafish can be an important model for investigating mechanisms of repair and re‐patterning in the cornea.