Alternatives for corneal endothelial tissue engineering

AbstractCorneal endothelial diseases are common almost everywhere in the world and have 3 main origins: primary diseases, largely dominated by Fuchs' endothelial corneal dystrophy (FECD), iatrogenic diseases which mainly complicate lens surgery, whether cataract or clear lens, but also other surgeries. The frequency of these complications is very low but the number of these surgeries being gigantic (probably around 50 million cases/year/worlwide), the number of post‐surgical bullous keratopathy remains important. Post‐keratoplasty endothelial failure (early or late) is the 3rd cause.All these diseases “consume” 50% of corneal grafts in the world and a large part of the population does not have access to any graft. The number of corneal donors is absolutely insufficient to meet the world demand and corneal bioengineering appears to be a realistic solution to complete the offer. Because of its relative simplicity and the demonstrated effectiveness of endothelial keratoplasty, endothelial bioengineering is logically the first to be developed. The Japanese team of 2 Kyoto universities (Prof. S. Kinoshita, N. Koizumi and N. Okumura) is a pioneer in this field and has demonstrated the effectiveness of injection therapy, which consists of cultivating mature endothelial cells from a small number of corneas from young donors, then injecting them into the anterior chamber of patients. The industrialization of the process is underway in 2 different start‐ups, one in the United States, the other in Japan. In addition to injection therapy, the bioengineering of endothelial grafts (Tissue engineered endothelial keratoplasty, TEEK), which consists of cultivating endothelial cells on a “corneo‐compatible” carrier to exactly reproduce a DMEK or a DSAEK, has passed the preclinical stage. This presentation will detail these different processes, their current limitations and the short, medium and long term perspectives. These Advanced Therapy Medicinal products (ATMP) are clearly revolutionizing corneal transplantation. By offering a new treatment for endothelial diseases, they will make it possible to redirect donor corneas to other corneal diseases that have no therapeutic alternative. Finally, this paper will also discuss the prospects of medical and medico‐surgical treatments for FECD, which are at the frontier of endothelial bioengineering.