Identification of a translatable rabbit model for corneal endothelial dysfunction

To explore the potential of an adult rabbit descemetorhexis model to recapitulate the damage to the endothelium and Descemet's membrane (DM) seen in humans.

Five corneas of 5 female New Zealand rabbits aged 24-26 months underwent 5-mm descemetorhexis; five unwounded corneas from 5 rabbits served as controls. Animals were followed up for 12-week and post-surgical clinical evaluation was performed using slit-lamp, macro images, and optical coherence tomography (OCT). Histological and immunohistochemical analyses were performed post-sacrifice.

Corneal transparency analysed by slit-lamp demonstrated that 2 weeks after descemetorhexis, all adult rabbits displayed grade 3 corneal opacity that was reduced to grade 2-3 and remained at this level until the study endpoint. Corroborating these results, quantitative analysis of macro images showed a significant reduction in corneal transparency during the entire follow-up period, with remarkable effect at 2 weeks (P < 0.05 vs. pre-surgery). Besides, OCT results showed a significant increase in corneal and stromal thickness and fibrosis at 4/8-week post-surgery (P < 0.05 vs. pre-surgery). By 12 weeks, rabbits maintained remarkable fibrosis (P = 0.013 vs. pre-surgery). Finally, histological and immunohistochemical analyses showed that the descemetorhexis group displayed absence of the DM-endothelium complex in the surgical center, which was associated with non-expression of Na⁺/K⁺-ATPase and Zonula occludens-1. An altered collagen matrix with myofibroblasts in the posterior stroma was also found in the surgical center compared with the other analyzed regions in both groups.

Our results indicate that descemetorhexis in adult rabbits could be a translatable corneal endothelial dysfunction (CED) model for studying the safety and efficacy of treatments for CED.