Stem Cells for the Treatment of Corneal Fibrosis

The cornea is the optically transparent tissue through which light first enters the eye. Together with the lens, the cornea bends incident light to focus it onto the photosensitive retina. Corneal fibrosis occurs in response to ocular trauma and infection and, by reducing corneal transparency, can impair or completely diminish this function, leading to vision impairment and blindness. Millions of people around the globe suffer from corneal blindness as a result of injury and infection. Fortunately, topical antibiotics and immunosuppressants help to prevent scars from forming. Should a scar develop, corneal transplant is a generally successful procedure that can restore sight to these patients. There are, however, drawbacks and limitations to the procedure in that immunological rejection of the donor graft and a limited supply of donor tissue prevent many patients from sustaining or receiving this treatment. The body of work presented here investigates stem cells as an alternative treatment for vision-impairing fibrotic wounds in the corneal stroma. First, I show that human embryonic stem cells are capable of differentiating to cells with a corneal keratocyte phenotype, a study that may lead to the development of a source of cells to repair damaged corneal tissue. I then show that a population of corneal stromal stem cells can be isolated in a biopsy-like procedure and prevent fibrotic wound healing in the mouse, presenting an autologous source of cells to treat corneal scars. Finally, I investigate a potential mechanism by which these stem cells prevent fibrotic wound healing via immunomodulation and the suppression of neutrophil infiltration to the wound bed. This work moves toward the development of an alternative to corneal transplantation that will bridge the gap between the supply and demand of donor tissue and provide a treatment option with a significantly reduced risk of failure due to rejection.