1. Background to Programme Area and Objectives

1.1 The Wound Healing Research Unit has a special interest in tissue repair processes in the eye and the human body. Processes involved in healing and scarring play a part in the pathogenesis or failure of treatment of most of the world's major blinding diseases. Previous work has been carried out in the unit on the use of short single applications of various anti-metabolites including beta radiation and anti-cancer agents such as 5-Fluorouracil (5FU) and mitomycin-C to prevent scarring.

1.2 This work has now been carried through to clinical use and is the subject of a large-scale clinical trial being carried out by the clinical wound healing team, which is also part of the Glaucoma Unit at Moorfields. There are also worldwide trials being carried out in the Far East (Singapore, National Medical Research Council), South America and Africa. Following laboratory work, we were also the first to use an antibody to transforming growth factor (TGF)-beta to prevent ocular scarring in humans. We have also shown for the first time, also based on laboratory experiments, that blinding scarring of the retina can be prevented using a simple intraoperative regimen of 5FU and heparin.

  2. Programme plan

Research will focus on the following areas

2.1 The role of growth factors, particularly TGF-beta and its effects on ocular scarring, and neutralising strategies (antibody now undergoing UK trials),

2.2 Apoptosis as a controlling phenomenon in wound healing,

2.3 The effects of anti-metabolites on a variety of fibroblast functions,

2.4 The role of matrix metalloproteinases (MMP), matrix and cellular motility in scarring,

2.5 New devices in ophthalmology including devices for glaucoma surgery,
epithelial healing, stem cells and effect on fibroblast healing

  3. Future development work in the programme during 2002/3

3.1 Our research has shown that surgery preserves the visual field much better than laser or medical treatment and as a consequence is now being performed much earlier in the course of the disease instead of waiting for medical treatment to fail. Surgery may also fail and the major cause of this is scarring at the operation site.

3.2 Under the direction of Professor Khaw a wound healing research programme has been established to identify the causes of scar formation after glaucoma surgery and clinical trials are currently being carried out on a number of methods of controlling scarring. These include an MRC funded clinical trial of a single dose of 5-fluorouracil applied during surgery to reduce scarring, specific inhibition and neutralisation of certain proteins that induce scarring and the exploration of inert biomaterials to form artificial drainage channels. These studies have all resulted in publications in high-impact journals. Many of these projects were launched following a systematic review of the effectiveness of medical treatment of glaucoma, highlighting the value of the Cochrane Eyes and Vision Group in identifying research needed to address gaps in the evidence base. This work will be continued in 2002/3 as a high priority benefiting many of the programmes of research detailed in this report.