Corneal epithelial cell bandage to treat persistent epithelial defect

Corneal would healing is essential to maintain the integrity of the cornea. In a healthy eye, after an insult to the ocular surface, the epithelial defect is repaired by a complex re-epithelialisation process. Healing may be delayed or halted in compromised conditions leaving the underlying stroma vulnerable to further trauma, infiltrates, infection, scarring and perforation. A persistent epithelial defect is defined as a defect that is not resolved after 2 weeks of standard treatment. There are risk factors that confound corneal epithelial wound healing including diabetic keratopathy, limbal stem cell deficiency, dry eye disease, neurotrophic keratopathy and herpetic infection to name a few. The current treatments for persistent epithelial defect can include lubricating eye drops, punctal occlusion to provide a more lubricious environment, bandage contact lenses, serum, tarsorrhaphy or amniotic membrane transplant. Standard treatments tend to be ineffective, prolonging patient discomfort and diminished visual acuity. Due to the complex nature of the disease, patients must be examined multiple times a week, with some patients requiring up to 90 visits a year. The economic impact of this on health systems is substantial.
We are developing an alternative treatment that involves transfer of corneal epithelial cells to the ocular surface directly via a soft contact lens. Our 'cell bandage' will enable rapid healing of the wound by the transplanted cells with the additional benefit provided by the contact lens element of the therapy of the protection from shearing forces that occur when blinking. We have proof of principle that the cell bandage functions to heal wounds in vitro but we need to test its effectiveness in a model using human eyes in the lab and its safety in a whole animal model. If the cell bandage provides favourable results we will continue to develop the product working with cell therapy manufacturers to determine a production method suitable for use in patients.

Persistent corneal epithelial defects pose a clinical challenge even for experienced ophthalmologists. Standard treatments tend to be ineffective, prolonging patient discomfort and diminished visual acuity. Due to the complex nature of the disease, patients must be examined multiple times a week, with some patients requiring up to 90 visits a year. The economic impact of this on health systems is substantial.
We propose a novel therapy involving the transfer of allogeneic human corneal epithelial cells (hCEpCs) containing p63 positively expressing cells. The transfer of cells will be facilitated by the use of a synthetic, poly-epsilon-lysine (PeK) based hydrogel as a carrier. The hydrogel will be optimised to support the attachment, growth and monolayer formation of hCEpCs. It will also provide the additional benefit of acting as a protective "bandage" for the first few days of treatment. We have data to show that our PeK hydrogels have excellent optical and suitable mechanical properties. We have shown that a hCEpC line attaches to the surface of the hydrogel. When applying the hydrogel epithelial side down onto an ex vivo porcine cornea with epithelial wound, the hCEpCs transfer from the hydrogel to the corneal surface so that the hydrogel can be removed and cells left to repair the wound.
This project aims to demonstrate that the cell transfer of hCEpCs using our PeK hydrogel is safe and suitable for use in patients with PED. We will define the optimum hydrogel formulation, determine if the hydrogel is safe for use on the ocular surface in a rabbit in vivo model, and answer the important question of how long transferred cells remain on the recipient corneal surface. This will have implications for the immunosuppression regime required. We will then develop the GMP process for manufacture of the cell bandage and determine whether this process effects cell efficacy in a rabbit model