Corneal Endothelial Progenitors for Ocular Regeneration: Translating Discovery into Clinical Therapies

The corneal endothelium is essential for maintaining corneal transparency through active fluid transport and barrier function. Corneal cell loss from disease, ageing or surgical trauma underlies a significant proportion of corneal blindness worldwide, with Fuchs' endothelial corneal dystrophy (FECD) and pseudophakic bullous keratopathy (PBK) representing the dominant clinical indications for corneal transplantation. While Descemet's membrane endothelial keratoplasty (DMEK) has substantially improved surgical outcomes, the procedure remains constrained by global donor tissue shortage. Regenerative medicine offers a compelling alternative by exploiting the latent proliferative and reparative potential of corneal endothelial progenitor populations. This review synthesises current knowledge on the foundational biology of corneal endothelial progenitor populations and the optimisation of expansion platforms to emerging preclinical and clinical evidence for both cell-based and pharmacological regenerative strategies. We also consider the outstanding translational challenges of potency standardisation, GMP-compliant manufacturing and regulatory navigation, as well as the longer-term potential of biomaterial-cell platforms and personalised iPSC-based medicine. The cumulative evidence positions progenitor-based approaches as viable and increasingly well-characterised alternatives to conventional donor transplantation, although their routine clinical use awaits the optimisation of manufacturing and regulatory platforms.