The anti-inflammatory drug diclofenac (DCF) relieves postsurgery eye pain and can delay corneal wound healing. This study established a human ex vivo eye model and demonstrates the delay of wound healing by DCF. Human and rabbit response to topical DCF (0.1%) was evaluated after an anterior keratectomy in 1) a New Zealand White rabbit in vivo study, and 2) ex vivo front of the eye models of rabbit and human, which included cornea and eye tissues that synthesize prostaglandins (iris, ciliary body, and conjunctiva). Rabbit corneal wound area in vivo was significantly greater because of DCF at 72 hr (1.72-fold) and 96 hr (2.8-fold), representing a 43% and 64% decrease in wound closure. In rabbit ex vivo eyes, wound area in the presence of DCF remained significantly greater: 1.74-fold at 48 hr and 2.6-fold at 72 hr, up to an 80% decrease in wound closure. In human eyes ex vivo, wound area in the DCF-exposed eyes was significantly greater (1.7-fold at 18 hr), representing a 50% decrease in closure. To further characterize DCF effects, gene expression changes specific to wound repair were evaluated in these ex vivo models. In rabbit cornea, DCF caused an upregulation of cytoskeletal remodeling and inflammation genes, and a decrease of immune response and stress response genes. In human cornea, DCF suppressed many cytoskeleton and remodeling genes and altered several apoptosis genes. This translational ex vivo front of the eye model to mimic in vivo findings strengthens the validity of the human ex vivo model and its potential for identifying clinical hazards.
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