Establishment and validation of an animal model for evaluating the effectiveness of corneal repair materials / 中国组织工程研究

ABSTRACT

BACKGROUND: Corneal repair materials can be used as an alternative of human donor corneas to repair corneal injuries, but their evaluation of effectiveness is necessary before entering clinical trials. Unfortunately, there is no standardized method for effectiveness evaluation until now. OBJECTIVE: To establish and validate a corneal fungal infection model in rabbits and the corneal transplantation method. METHODS: Twelve New Zealand White rabbits were selected to establish a corneal fungal infection model in the left eye (experimental) and a normal control in the right eye. Two weeks after modeling, acellular porcine corneal stroma was transplanted into the left eye. After transplantation, slit lamp microscope test, corneal thickness detection, intraocular pressure measurement, confocal microscopy test and optical coherence tomography were performed. Then the degree of transparency, degree of epithelium healing, degree of edema, degree of corneal neovascularization and degree of material thawing were evaluated. The corneal pathological sections with hematoxylin-eosin staining were observed at 3, 6 and 12 months after surgery. RESULTS AND CONCLUSION: (1) The corneal thickness increased significantly at 1 month after transplantation, varied slightly within 3-6 months, and became close to the normal value at 1 year. (2) The intraocular pressure of the left eye was close to normal eyes. (3) Findings from the optical coherence tomography showed that the repair materials fit well with the implantation bed at 7 days after transplantation; the transplanted area was fully covered with epithelial cells at 6 months after transplantation, and the uniform thickness of the repair material in the transplanted area was detected; the grafted cornea was restored to normal cornea at 1 year after transplantation. (4) Under the confocal microscope, the repair materials in the transplanted area were evenly spread at 1 month after transplantation; few cells migrated into the transplanted area at 6 months after transplantation; the density of epithelial cells was increased, and there were migrated cells in the transplanted cells, but the cell number was less than that of normal eyes at 1 year after transplantation. (5) The corneal repair material was almost completely transparent at 1 year after transplantation, indicating its effectiveness in the treatment of infectious corneal ulcers. No rejection occurred, indicating that the corneal healing material is well-curative. (6) At 3 months after transplantation, a large number of stromal cells migrated to the corneal substitute, and the collagen fibers in the transplanted area were arranged neatly and densely without obvious scarring and degradation. At 6 months after transplantation, the transplanted area basically recovered. At 1 year after transplantation, the transplanted area was fully restored to the normal cornea state with good biocompatibility. Our experimental findings indicate that the rabbit model of corneal fungal infection and the corneal transplantation method can be used to evaluate the effectiveness of such corneal materials.