Experimental models of corneal endothelial cell therapy and translational challenges to clinical practice

The human corneal endothelium (CE) is a post-mitotic monolayer of endothelial cells, thought to be incapable of in vivo regeneration. Dysfunction of the CE is a commonly cited indication for corneal transplantation, with corneal blindness being the fifth most common cause of blindness globally. In 2012 alone 184,576 corneal transplants were performed in 116 countries (Gain et al., 2016). Presently, outcomes following human corneal transplantation have been reported to have over 97% success rate in restoring the recipient's vision (Patel et al., 2019). However, the continuing demand for cadaveric human corneas has driven research into alternative sources of CE and with the advent of protocols to produce cultured hCECs there is now the potential for cell therapy to regenerate the damaged CE. This review aims to examine the merits and limitations of different types of human and animal models used so far to test the concept of CE cell therapy.