CORNEA

Diseases of the posterior surface of the cornea (the corneal endothelium) are common, induce irreversible corneal edema and can currently only be treated by transplantation of a deceased donor cornea. Unfortunately, the number of donors is insufficient to treat all the patients waiting (1 to 70). In Japan, a clinical trial of endothelial cell therapy has demonstrated, in 11 patients and with a 5-year follow-up, the efficacy of transplantation with endothelial cells (ECs) from young donors, grown in vitro. The diffusion of this therapy is limited mainly by the low number of donors under 30 years of age. ECs from the much more numerous older donors do not proliferate sufficiently in vitro and cultures rarely result in the formation of functional endothelium. We hypothesize that a subpopulation of senescent ECs, already identified in the literature and in our preliminary work, are the main barrier to this in vitro proliferation by transmitting arrest and trans-differentiation signals to the whole culture. The CORNEA project brings together 3 laboratories with expertise in (1) senescence and its therapeutics, (2) biology, engineering and imaging of corneal grafts, and (3) large-scale proteomic analyses. CORNEA will identify markers to characterize senescent cells and their consequences by establishing an atlas of factors secreted by senescent ECs and by determining how the presence of senescent ECs directs the trajectory of cultures. CORNEA will also identify effective anti-senescence molecules to enable culture for cell therapy from the most common donors (50-80 years old). To reduce the burden of corneal blindness, CORNEA will overcome the major barrier to future treatment of corneal endothelial diseases.