Corneal endothelial cells decline – A review of recent findings from molecular and clinical research

Corneal endothelial cells (CECs) are essential for maintaining corneal transparency by regulating stromal hydration through active ion transport. Unlike other epithelial cells, human CECs are arrested in the G1 phase of the cell cycle and do not proliferate in vivo. Recent molecular studies reveal that this arrest is not due to senescence but rather to active regulation by pathways involving NF-κB, the c-Jun N-terminal kinase (JNK), and the p38 mitogen-activated protein kinase (p38 MAPK) JNK/p38 pathway. Experimental modulation of these regulators has successfully induced proliferation in vitro. Clinically, CEC density declines naturally with age but is significantly accelerated by surgical trauma (e.g., cataract surgery), disease (e.g., Fuchs endothelial corneal dystrophy), and inflammation. Therapeutic strategies such as Descemet membrane endothelial keratoplasty (DMEK), cell-based therapies, and pharmacologic treatments-including Rho-associated kinase (ROCK) inhibitors-are being developed to restore endothelial function without full-thickness corneal transplantation. These recent findings suggest a paradigm shift: from considering CEC loss as irreversible to targeting molecular pathways that could potentially restore CEC regenerative capacity.