Why do people lose their sight to AMD?

Age-related macular degeneration - AMD - is the leading cause of vision loss in people over 50 in the Western World.(1) There is no cure. In the UK, estimates suggest the condition affects over 2 million people, with numbers set to rise dramatically as our population ages.(2) Researchers are trying to pinpoint the molecular pathways that damage the eye in AMD. Their work may ultimately lead to new treatments.

What's the problem and who does it affect?

Millions worldwide are losing their sight to AMD

People tend to value their eyesight above all other senses. Sadly, vast numbers of us face the prospect of losing our vision to AMD - age-related macular degeneration.

AMD is a major health problem, affecting an estimated 25-30 million people worldwide.(3) Most sufferers are over 50 years of age. With our ageing population, their numbers are rising fast.

AMD has a devastating effect on people’s quality of life. Typically, the first thing they notice is some blurring or distortion in their central vision. When the disease becomes advanced, a blank patch or dark spot right in the centre of their field of view causes huge difficulties.

Most people with advanced disease can’t read, write, watch television, drive or conduct many other everyday tasks that the rest of us take for granted. They can’t even see the faces of loved ones properly. Many worry about losing their independence.

There is no cure for AMD. New treatments can prevent the progression to blindness, but they work for only a minority of patients, around 10%, who have a particular type of advanced AMD.(4)

What is the project trying to achieve?

What causes damage to the retina?

Vision loss in AMD results from progressive damage to the macula, which is part of the light-sensitive retina, at the back of the eye. This damage typically goes unnoticed until it becomes so bad that people start to lose their vision.

We have no firm understanding of exactly what causes the damage to the retina, and opportunities for early diagnosis are limited. Age is the main risk factor associated with AMD, but it’s not clear why some people develop the condition while others do not.

In this project, researchers aim to increase our understanding of the disease processes that lead to AMD. They are focusing on the role of a molecule called RAGE, which seems to be important in changes that take place in the eye with ageing. They suspect that harmful signals from RAGE may lead to the damage found in the eyes of people with AMD, possibly by provoking inflammatory responses. They are using state-of-the-art techniques to study the effects of RAGE on a molecular and cellular level.

What are the researchers' credentials?

The Project Leader, Professor Alan Stitt, has been instrumental in the establishment of a large, internationally recognised centre of excellence in experimental ophthalmology. He is Scientific Director of the Centre for Vision Science, and his team has grown in size exponentially over the last 6 years.

The team’s fully integrated programme of research tackles the major causes of blindness in the UK. Studies range from investigations into the fundamental causes of blindness to clinical trials of new treatments. All work is heavily focused on addressing patients’ needs.

Prof Stitt has published over 80 scientific manuscripts. AMD is a major focus of his research and that of his centre. On a personal level, Prof Stitt’s mother has experienced severe vision loss from AMD, which gives him an extra motivation to understand the condition and try to develop new ways to treat it – as early as possible in the disease process.

Who stands to benefit from this research and how?

Could new drugs help save people’s sight?

The researchers hope to reveal fundamental new information about the molecular and cellular processes that damage the retina, and cause vision loss, in AMD. Their focus on the possible role of RAGE is timely and important. A range of drugs that target RAGE, and modify its function, have already been developed – some are currently undergoing preclinical tests for possible use in the treatment of diabetic complications and age-related diseases.

So, if the researcher’s suspicions are right, and RAGE does play in key role in damaging the eye, these drugs might also help in AMD. Further laboratory work would be needed, but the researchers have a strong track record in building on basic discoveries and then taking new treatments through clinical trials.

The long-term aim is to find a new treatment that prevents damage to the retina in AMD, so saving people’s sight. This could help reduce the enormous socio-economic costs associated with AMD, and avoid the devastating effects that vision loss has on people’s lives. If RAGE is important, then a new treatment may not be so far away.

References

1. de Jong (2006) Age-related macular degeneration. New England Journal of Medicine; 5;355(14):1474-85

2. Owen et al. (2003) How big is the burden of visual loss caused by age related macular degeneration in the United Kingdom? British Journal of Ophthalmology 87:312-317

3. Gehrs et al. (2006) Age-related macular degeneration--emerging pathogenetic and therapeutic concepts. Annals of Medicine, 38(7):450-71

4. Andreoli and Miller JW (2007) Anti-vascular endothelial growth factor therapy for ocular neovascular disease. Curr Opin Ophthalmol ;18(6):502-8.