Pluripotent stem cells, cornea fate and physiopathology

Abstract

SummaryThe human corneal surface epithelium is continuously repopulated by limbal stem cells (LSCs). Limbal Stem Cell Deficiency (LSCD) can lead to corneal opacity and vascularization, with consequent visual impairment or blindness. Chemical or thermal trauma and congenital diseases, such as congenital aniridia, can lead to LCSD by destruction of the LSC niche. Grafted autologous limbus or cultivated LCS can restore the vision, unless the two eyes are affected. We have recently developed novel culture systems to reprogram hair follicles into induced pluripotent stem cells (iPSCs) and differentiate them into LSC that could become an alternative to animal models for drug cytotoxicity and an alternative autologous source to the shortage of post‐mortem cornea transplantation.Moreover, we identified miR‐450 as specific repressor of PAX‐6, the eye master gene responsible for proper embryonic eye formation and LSC pool maintenance. As most of the aniridia patients carry mutations on PAX‐6 that lead to haploinsufficiency, we are testing if manipulating the level or activity of miR‐450 could be used as a therapeutic strategy in aniridia.Thus, iPSCs are valuable for modeling corneal pathologies, and pave the way for future therapy.