Cornea Regeneration using limbal tissue explants

This  project, led by the University of Sheffield in collaboration with the L.V.Prasad eye clinic in Hyderabad,  is developing  corneal repair materials and  procedures that offer a step change in availability and affordability. Synthetic electrospun membranes will repair donor tissue.  Phase I clinical trials to demonstrate patient safety are underway.

Image courtesy of University of Sheffield.

The Electrospinning Company has supplied biodegradable synthetic membranes to a team, led by Professor Sheila MacNeil of the University of Sheffield, who are developing affordable corneal surface regeneration techniques in collaboration with Dr Virender Sangwan at the L.V.Prasad eye clinic in Hyderabad, India. The concept that a corneal epithelium can be regenerated on the eye with very small pieces of tissue  has been demonstrated using  human amniotic membrane (current state-of-the art) and a synthetic sterilised biodegradable membrane has been developed and evaluated in vitro. Safety has been demonstrated in an in vivo model. A phase I clinical trial has been initiated at the L.V. Prasad eye clinic in Hyderabad, India.

A publication in Biomaterials titled “Simplifying corneal surface regeneration using a biodegradable synthetic membrane and limbal tissue explants”, on which Dr Rob McKean is a co-author, describes how corneal cells have been successfully cultured on a synthetic sterilised biodegradable membrane either from cells isolated in a laboratory or from cells grown out from very small pieces of tissue. A second publication in the British Journal of Ophthalmology describes the pre-clinical tests that showed that membranes could be safely applied to rabbit eyes (the standard model) without inducing local or systemic toxicity and that the membranes broke down completely within 29 days.

Specialist stem cells at the front of the eye have the job of keeping the cornea clear and scar-free. If someone loses the population of cells that renew this corneal epithelium then surrounding scar type tissue grows over the eye with resulting loss of vision and pain. For some 15 years in a few specialist centres around the world it has been possible to take a small piece of tissue from the unaffected eye, expand these cells in a specialist laboratory and then transplant these back to the cornea, applying the cells to the damaged cornea on pieces of human donor amniotic membrane. This requires access to a well-run tissue bank to access the donor amniotic membrane, as well as access to clean rooms, specialist clean room staff to culture the cells and considerable surgical skill.

The Sheffield-India collaboration, funded by the Wellcome Trust Affordable Healthcare for India programme, is aiming to simplify this technique to make it available to ophthalmic surgeons worldwide. There are two steps in the thinking:

  • Can a new corneal epithelium be regenerated from a very small piece of the unaffected eye?
  • Can a synthetic membrane be produced as an alternative to the human amniotic membrane which can be stored and ready for use by surgeons anywhere?

Source: P. Deshpande, C. Ramachandran, F. Sefat, I. Mariappan, C. Johnson, R. McKean, M. Hannah, V. S. Sangwan, F. Claeyssens, A. J. Ryand, S. MacNeil “Simplifying corneal surface regeneration using a biodegradable synthetic membrane and limbal tissue explants” Biomaterials 34, 21 (2013), pp. 5088–5106.

C Ramachandran, V Sangwan, I Ortega, U Bhatnagar, S Mulla, R McKean, S MacNeil, Synthetic biodegradable alternatives to the use of the amniotic membrane for corneal regeneration: assessment of local and systemic toxicity in rabbits </a>“.British journal of ophthalmology 2018