Acute high intraocular pressure induced by vitreous cavity infusion: an animal model to evaluate corneal endothelial injuries.

Abstract

Elevated intraocular pressure (IOP) is a critical factor in corneal endothelial cells (CECs) injury, yet the precise mechanisms remain poorly understood due to confounding variables in clinical studies. This study developed an acute high IOP model in New Zealand rabbits by vitreous cavity infusion to investigate the effects of high IOP on CECs. The observed anterior chamber shallowing and anterior shift of the lens and iris suggest that this model mechanistically mimics acute angle-closure glaucoma (AACG), particularly those cases driven by a posterior pushing mechanism. The model induced stable IOP elevations up to 60.25 ± 1.83 mmHg, resulting in transient corneal edema and significant CEC damage, including cell swelling, irregular morphology, and disrupted barrier function proteins. Over 14 days, a progressive and significant decrease in endothelial cell density (ECD) of 11.8 % was observed, accompanied by compensatory morphological changes, indicating irreversible damage despite edema resolution. Mechanistically, this cell death is driven the intrinsic mitochondrial apoptotic pathway, evidenced by an increased BAX/BCL-2 ratio, cytochrome c upregulation, and subsequent activation of Caspase-9 and Caspase-3. Furthermore, increased expression of senescence markers (P16, P21, P53) was also noted. This model, without anterior chamber invasion, provides a robust platform for future mechanistic studies and evaluation of therapeutic interventions, underscoring the critical need for rapid and effective IOP management in clinical practice to preserve corneal endothelial integrity.