Corneal Endothelial Stem Cells for Treatment of Corneal Endothelial Dystrophies

DESCRIPTION provided by applicant Corneal clouding caused by failure of the corneal endothelial deturgesence mechanism affects over million people in the US and well over million people worldwide It is the most common corneal disease and is historically a common cause of blindness Surgical treatment by corneal grafting has been successful when available but is limited by the availability of donor material andlt k corneas yr and by surgical facilities ad talent RashmiVu and The Ohio State University have jointly isolated expanded and confirmed a plentiful source of human corneal endothelial stem cells hCESCs and conceptually developed a procedure that would allow successful implantation into the eye where the cells can repair or regenerate the endothelium and thereby restore corneal clarity This bypasses the need for other corneal donor material surgical facilities or highly trained surgeons and can be made available worldwide Preliminary research shows that these hCESCs have both endothelial and stem cell characteristics they are precursor cells and that they migrate and adhere to damaged endothelium ex vivo The remaining feasibility steps to be explored in this Phase I are a to test whether these cells lead to the repair of alkali damaged endothelium in vivo and b to start determining mechanisms of action adhesion vs sprouting induced endogenous vs direct autologous healing in both scratch damaged and chemically damaged corneal endothelial cell layers The team will perform the in vivo study in a murine model using hCESCs and the mechanisms analysis in an in vitro human cell based model using hCESCs The expected outcomes are that treated eyes in the murine study will show marked healing compared to controls and that at least one mechanism of action for healing will be determined PUBLIC HEALTH RELEVANCE Human corneal endothelial deturgescence affects more than four million people in the US and more than million people worldwide It is the most common corneal disease and is historically a common cause of blindness Limited surgical treatment is available due to the limitation of donor cornea RashmiVu LLC and The Ohio State University have jointly isolated expanded and confirmed a plentiful source of human corneal endothelial stem cells hCESCs and conceptually developed a procedure that would allow successful implantation into the eye where the cells can repair or regenerate the endothelium and thereby restore corneal clarity