The collagen matrix in corneal pathology, and the effect of new therapies for loss of transparency and refractive status

The cornea is the transparent window at the front of the eye through which we see the coloured iris and black central pupil. It is made up mostly of a protein called collagen and forms part of the tough outer shell of the eye. Most of the outer shell is opaque and white in colour, but the cornea has evolved to transmit light. Evidently, the transparency of the cornea is absolutely essential for vision, and it is believed that the reason why the cornea, unlike all other collagen-containing tissues in the body, is transparent, is because of the special size and arrangement of the collagen and the special properties of the interspersed cells. One purpose of our proposed investigation is to discover precisely how the arrangement of the collagen and the properties of the cells allow the cornea to be transparent. We will then examine how certain treatments act to restore transparency where it has been lost. In addition to allowing light into the eye, the cornea is also curved in a special way to help focus the incoming light on the retina. Again, it is believed that aspects of the collagen organisation might influence this curvature and be important for corneal astigmatism and the recovery of good vision after corneal surgery (including new refractive surgeries such as LASIK). The research is to be carried out using a range of techniques, including synchrotron x-ray technology and several high powered microscopical methods. It will be carried out by a team of Biophysicists in Cardiff, but will involve a number of scientists and clinicians from around the world.

The cornea is the main refractive component of the eye. Its dioptric power and efficiency in conveying an image to the retina free of astigmatism, both depend on its shape and surface topography. These, together with the cornea?s remarkable transparency, depend on the organisation of its constituent collagen molecules and fibrils, about which many questions remain unanswered. Corneal problems are a leading cause of visual impairment worldwide, and are an increasing drain on the NHS. Thus it is imperative to understand the reasons for transparency loss and for pathological and post surgical ectasia. Our work aims to do just this, and ascertain the structural basis for the restoration of corneal transparency and refractive status by a number of new therapeutic strategies. The objectives of this proposal are:
? To model corneal transparency at the cellular and fibrillar level and ascertain the potential of keratocyte stem cell therapy in the restoration of matrix structure and tissue transparency.
? To produce a full 3-D structural map of the healthy human cornea and understand the roles of specific lamella structures in determining its biomechanical properties, refractive status, pathological change and surgical treatment.
? To understand the cause of corneal ectasia and its treatment by ultraviolet crosslinking.
The principal method will be synchrotron x-ray scattering. This will be supplemented by microscopy (phase contrast, electron and multi-photon confocal), spectrophotometry, ocular coherence tomography, videokeratography, finite element analysis and computer modelling of light scattering.