St Paul's Eye Appeal
Research - Glaucoma
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Glaucoma remains a major cause of blindness in the elderly. In fact, after cataracts, it is the second leading cause of vision loss in the world with over 65 million people suffering from the disease.
In the normal eye, a fluid called aqueous humour flows continuously into the front chamber of the eye where it provides nutrients to the anterior ocular tissues. The used humour then starts to drain from the anterior chamber (AC) via a tissue known as the trabecular meshwork (TM).
From the TM the humour flows into a structure called Schlemm’s canal and from there it is removed from the eye by the blood stream. As waste aqueous humour flows out of the front of the eye it is replaced by similar volumes of fresh solution. This normal fluid cycle helps maintain the eye’s intraocular pressure (IOP) at a constant level.
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In primary open-angle glaucoma (POAG), which is the main form of glaucoma in the UK, the flow of waste aqueous humour through the TM is reduced. As the flow of fresh humour into the eye remains at it normal level, there is an increase in the total volume of humour in the eye leading to an increase in the eye’s IOP. If untreated, this elevated IOP can damage the nerve fibres in the retina and optic nerve resulting in reduced vision and eventually blindness.
Whilst medications exist to prevent the progression of glaucoma, they do not act against the compromised outflow system which is the root cause of the disease. For example, many of the anti-glaucoma medications we use, lower eye pressure by reducing the production of fresh aqueous humour and this in turn causes further long-term problems in the outflow system.
Our glaucoma research therefore currently centres on investigating how the outflow pathway in the eye becomes compromised.
We have already found that glaucoma is associated with a loss of cells from the TM part of the outflow system. We believe that this leads to failure of the outflow system as these cells are required for it to function efficiently.
We have also found that some TM cells change their shape in glaucoma. The shape of a normal TM cell is maintained by a cytoskeleton of actin fibres that extend across the cell. However, some TM cells reorganise their cytoskeleton so that their actin filaments cross link with one other. These ‘cross-linked actin networks’ (CLANs) can aggregate within a cell to create a geodesic structure.
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Normal actin fibre arrangement in trabecular meshwork cells imaged using confocal microscopy |
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CLAN in a trabecular meshwork cell imaged using confocal microscopy |
The use of similar geodesic structures both in nature (pollen grains) and commercial architecture (roof over the British Museum courtyard) has shown them to be physically strong units with minimal contractile ability. If TM cells do become less contractile in glaucoma, this would reduce the flow of humour through the outflow system, increasing IOP.
Professor Grierson and his team in the Ophthalmology Unit, were the first in the world to image CLANs in tissue from inside the human body.
CLANs are known to change the shape, function and life cycle of cultured cells. Experts from around the world had previously argued whether such structures actually existed inside the body or whether they were just a theoretical possibility. Our team's confirmation of their presence in part of the eye compromised in glaucoma - the trabecular meshwork, could well be the cellular fingerprint leading to new treatments for this disease.
It had been predicted that the search to determine whether CLANs existed inside the eye would take the Liverpool team 6 months to complete, but unequivocal confirmation eventually took several years. Taking into consideration the size of the structures that Professor Grierson and his team are looking at, one can fully understand why it took so long; the CLANs can be as thin as 1 micrometre (a micron or 1/1000th of a millimetre). There was of course the problem of discovering the best technique to view the CLANs with - not easy if you don't know whether they actually exist.
Although this is a tremendous breakthrough in our research, a lot of work remains to be done.
The findings so far have already opened new doors in the search for finding new treatments for common eye diseases. Now Professor Grierson has identified these CLANs, his dedicated team are working to understand why they form, potentially causing the cells to become rigid and preventing them from working as they should. His team also needs to determine whether CLAN formation is central or incidental to eye disease. To take this work further he needs additional specialist personnel and equipment that will enable him to probe further into the molecular working of trabecular meshwork cells.
Key to our analysis of CLANs in glaucoma if the technique of confocal microscopy. This is a special technique which allows thick, intact parts of the eye to be optically sectioned and imaged as a series of separate thin volumes suitable for analysis. Confocal microscopy was used to make the images of trabecular meshwork cells shown on this page and is also integral to our other research programmes.
Professor Grierson's team continues to perform basic and applied research directed at understanding both why cells are lost from the outflow system in glaucoma and why changes occur in their structure. If we could find the key to cell loss and altered cell behaviour it would unlock new preventative treatments for glaucoma.
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