Ocular surface diseases include several blinding disorders that affect the cornea and conjunctiva - the front surface of the eye. As a national referral centre, Moorfields receives relatively large numbers of patients whose ocular surface disease is so severe that they have lost their sight.
Moorfields Eye Hospital and the UCL Institute of Ophthalmology have a long track record in the investigation of ocular surface disorders. We have focussed on diseases that result in the dysfunction and death of so-called limbal epithelial cells that can lead to chronic corneal ulceration.
Our objectives are:
- improving limbal epithelial stem cell (LESC) therapy and developing other novel cell-based therapies to treat ocular surface disease,
- the prevention of corneal transplant rejection by the host immune system, and augmentation of transplant endothelial function, post-grafting, by ex-vivo genetic modification pre-graft
Direct molecular quality enhancement of donor corneas
Some 500 corneal transplants are undertaken at Moorfields each year and our aim is to prolong the lifespan of the donor cornea cells that are transplanted into patients with blinding corneal disease.
We are developing a method to do this by modifying donor cornea cells in the laboratory before transplanting them into patients’ eyes. This should reduce – and possibly remove – the need to replace transplants and, in the future, the need for a transplant may be eliminated altogether by treating the patient’s own cornea with this type of technique.
Stem cell transplantation for limbal failure
The Cells for Sight Transplantation and Research Programme is at the forefront of using stem cells to tackle eye diseases that were previously untreatable. Where permanent blindness used to occur, we can now help some patients with genetic disorders, eye inflammation or chemical burns who have scarring and opacity of the cornea.
We are developing the optimum process to provide a graft with the highest possible stem cell content. Successfully transferring such a graft from the laboratory to the surface of a patient’s eye in the operating theatre has been a huge obstacle but we are now overcoming this by developing a novel bioengineered substance to carry the cells.
If the disease occurs in both eyes, stem cells from a patient’s own eyes cannot be used and we have previously had to rely on donor tissue which can therefore be rejected by the recipient. However, we have now developed methods of isolating stem cells from a variety of human tissues, such as the patient's own mouth, and hair follicles from their scalp, so providing a source of cells that will regenerate the surface of the eye but will not be a target for immune rejection.
Treating blinding scarring conjunctival diseases by selective new treatments
Blinding scarring conjunctival diseases are immune-mediated – that is, they are caused by abnormal activity of the body’s immune system. We are currently investigating the genetics and specific proteins in the ocular surface that are the targets for this immune response. At present, very potent immunosuppression drugs are necessary to stop disease progressing in most patients and we are evaluating new drugs and drug combinations that are more effective but also more specific, in order to reduce the incapacitating or life-threatening side-effects of the drugs in current use.