Rationale: 45 million individuals worldwide are bilaterally blind, among them 4.9 million are suffering from corneal defects. Corneal disorders are consequences of congenital diseases, or environmental insults such as physical injury, viral infection, chemical and thermal burns. The general result is corneal neo-vascularization that leads to loss of corneal transparency and blindness. Corneal transplantation is widely used with high success at the short term but is limited by the shortage in post mortem cornea and immunorejection prevalence is significantly increasing with time within the first 5 years. Therefore, there is a major need for alternative allo- or autologous sources for corneal cell therapy. Background: Oral epithelial cells, mesenchymal stem cells, hair-follicle stem cells and embryonic stem cells were investigated for their therapeutic potential for corneal diseases. However, only partial success has been achieved by the use of these cells since they were not able to uniformly commit into corneal epithelial cells and/or no experimental data have been provided to demonstrate their ability to stratify and reconstitute in vitro a corneal tissue or displayed abnormal thickness and barrier function. Artificial cornea is an alternative acellular solution that is suggested only for patients with complex ocular diseases who are at high risk for donor graft failure. These complicated surgeries unfortunately allow limited vision improvement and are expensive. Innovative product: we propose here to design a standardized and reproducible technology to produce in large amount "ready to use" cornea from human pluripotent stem (induced or embryonic) cell lines. We will take advantage of the unlimited growth capacity of these cells and their pluripotent ability to differentiate into any cell type. As a proof of concept, we have recently developed an efficient technique to generate corneal cells expressing putative corneal-specific markers from either human embryonic stem cells or human induced pluripotent stem cells. We have shown that these corneal cells are able to stratify in vitro for the production of a corneal tissue. Potential applications of the innovative product: the finalized product will be used in two main applications: a. corneal regenerative medicine: here, we aim to produce unlimited cornea from pluripotent stem cells. Such tissue will serve as “ready-to-use” source to be transplanted immediately into injured eye as allo-graft. This product will be easily accessible for surgeons around the world, standing by for grafting into patients. In addition, for patients presenting immuno-rejection problem, autologous cornea will be produced directly from their own cells. b. cellular model for cosmetical toxicity and drug testing: the corneal tissue obtained from pluripotent stem cells should become a valuable tool to perform, in a reproducible and physiological manner, toxicity assays of cosmetic products and pharmacological tests of drugs. The EU Cosmetic Directive lead to the ban of animal testing for cosmetic ingredients (acute tests). Major efforts are still made to find reliable and relevant alternative methods to eye irritation testing. So far, quite unsuccessfully as no suitable model is yet established. Our reproducible in vitro tissue model will allow predicting the safety and efficacy profiles of actives and formulations. Specifically, it will be used in ocular irritation assays, as tests for corneal permeability and metabolism and mucin production. To be done within 2 years: our current goals are (1) to standardize the quality of iPSC/huESC-derived corneal tissues, (2) to evaluate their therapeutic potential in vivo, (3) to demonstrate that this model may serve as a useful in vitro tool for toxicity assays, thereby allowing the reduction in animal testing.