Regenerative therapies for the ocular surface

Abstract

Integrity of ocular surface depends on adequate tear film and stability of the surface epithelium consisting of two specialized phenotypically different epithelial cells, the central transparent corneal epithelium and the peripheral conjunctival cells, separated by a more specialized transition zone, called the limbus. Similar to the epithelial regeneration in other parts of the body, the corneal epithelium is regenerated from the stem cells located in limbus. Severe chemical burns and other diseases can cause damage to the limbus, resulting in a condition called Limbal Stem Cell Deficiency (LSCD). Effective therapeutic modalities for this vision-threatening condition include use of human amniotic membrane, replenishing the stores of limbal stem cells by limbal transplantation. However last decade has witnessed the use of ex-vivo expanded sheet of limbal epithelial cells for ocular surface reconstruction in such cases. Our group has established a simple, feeder-cell free, cost-effective way of culturing the corneal epithelium from limbal tissues within 2 weeks, using human amniotic membrane as a carrier. The interim results of a clinical trial involving 700 patients with severe unilateral and bilateral LSCD revealed 70% and 50% success at the end of 3 and 5 years respectively. For patients affected by bilateral disease, options include use of allogenic tissues with immunosuppressive therapy or use of autologous alternative sources of epithelium like oral mucosal epithelium, both of which show limited success. The pre-requisites for cell therapy are that the desired cells should be grown in sufficient amounts, should survive, integrate and network with the host tissues and cause no harm to the recipient. All these criteria are fulfilled when limbal epithelial cell therapy is used for ocular surface reconstruction thus making it a successful model in the emerging field of regenerative medicine.