Abstract

Keratoconus (KC) is a progressive corneal ectasia characterized by stromal thinning and conical protrusion, often leading to significant visual impairment. While the primary pathology is often attributed to the corneal stroma, the role of the corneal endothelium in KC progression remains a critical area of investigation. Corneal Endothelial Cells (CECs) are vital for maintaining corneal transparency through their active regulation of corneal hydration, a process heavily dependent on precise cell volume regulation (CVR). This study investigates potential disorders in CEC volume regulation in keratoconic corneas compared to healthy controls. Using an in vitro model, CECs were subjected to osmotic stress, and their volume dynamics were monitored. The results indicate a significant impairment in the regulatory volume decrease (RVD) mechanism in KC-derived CECs, suggesting a lower capacity to extrude osmolytes and restore baseline volume following swelling. This functional deficit in CVR is hypothesized to contribute to the subclinical endothelial dysfunction observed in KC, potentially exacerbating corneal edema and contributing to the overall pathophysiology of the disease. These findings highlight the CECs as a novel therapeutic target for stabilizing corneal function in keratoconus.