Scarring and contraction in and around the eye are very important causes of visual morbidity, and play a part in the failure of treatment for most major blinding diseases today. Examples include lens capsule contraction, proliferative vitreoretinopathy, macular scarring, corneal scarring, scarring following glaucoma surgery, and eyelid and orbital contraction following disease.
This theme also includes diseases such as severe retinopathy in premature babies, for which there are no effective treatments and which results in a lifetime of blindness. Researchers at Moorfields and the UCL Institue of Ophthalmology work on virtually all of these conditions and aim to develop appropriate delivery and formulation systems through this theme.
We are focussing, in particular, on developing new surgical techniques based on laboratory understanding of biological responses. These include: the role of growth factors and their effect on ocular scarring; the cellular and molecular basis of cell motility (spontaneous movement) and scarring; and the basic biology and therapeutic use of ocular stem cells in, for example, the prevention of scarring, and in tissue reconstruction and regeneration.
Our objectives are:
- To research the processes involved in scarring and the failure of cells to regenerate
- To work with several other themes to develop therapies using stem cells to repair the retina and optic nerve head
- To develop new drug delivery systems, with colleagues at the School of Pharmacy and Moorfields Pharmaceuticals, to reduce scarring after eye surgery
Why scarring is important
Our focus is the efficient development of new clinical treatments to control scarring (fibrosis) after surgery and disease. The causes of fibrosis are complex and themselves contribute to many human diseases, including every major blinding disease. There is a large unmet need for anti-scarring therapies that could be used for disease treatment and to manage healing after surgery. Preventing scarring also helps the body to regenerate, and encourages stem cells to restore the eye.
Improving anti-scarring treatments
Administration of anti-cancer agents directly into the eye after glaucoma filtration surgery to control fibrosis (and so manage healing) is currently the best clinical treatment available. There are, however, many side effects because repeat injections of high doses that are naturally and rapidly cleared in some regions of the eye (eg the conjunctiva) are nevertheless toxic locally and systemically (throughout the body).
To address toxicity, we have discovered that repeat injections of a drug called metalloprotease inhibitor (MMPI) greatly reduce scarring - and without the toxicity of anti-cancer agents.
New methods of drug delivery
To address tissue-specific pharmacokinetics (what the body actually does to the drug, as opposed to what the drug does to the body), we have developed a novel, small, resorbable tissue tablet to release MMPI locally at the fibrotic site. Our results indicate a way of developing the MMPI tablet to treat post-surgical fibrosis that has a very good chance of success. If post-surgical scarring can be controlled and the surgery is successful long term, we have shown in large trials that it is possible to halt the progression of glaucoma.
We have also developed a prolonged dosage form of an antibody, a protein-based medicine. Antibodies are usually administered as injections, but we have developed a tablet form, whereby a single tablet can be placed at the site of surgery, and remain biologically active over an extended period of time. A recent study has shown this new antibody tissue tablet to be more efficacious than any treatment currently being used clinically.
Since glaucoma is the second leading cause of blindness worldwide, the development of these new medicines, which will simplify both surgical and post-surgical procedures, will potentially enable glaucoma filtration surgery to be carried out more widely and so stop the progression of glaucoma in many more patients.