February 8, 2011
Australian Donors Aid Breakthrough In Eye Disease
An international scientific team has announced the discovery of a trigger for the commonest form of vision loss and blindness in older people western society.
Their findings, achieved with help from Australian eye donors, could lead to ways to treat a disease that has until now been regarded as untreatable.
Researchers from Australia and the United States reported in the current issue of the journal Nature their finding that a critical enzyme is lacking in patients suffering untreatable age-related macular degeneration (AMD).
Age-related macular degeneration (AMD) is as common as cancer in industrialized countries, affects one in every seven Australians over 70 and is a leading cause of blindness in the elderly. The macula is the central part of our retina that gives us our acute vision, our ability to read and recognize faces.
Working across 23 different universities and institutes, including four in Australia, the team demonstrated that the enzyme DICER-1 is reduced in the eyes of those suffering the dry form of AMD, resulting in a condition which causes stress and premature death to the vision cells.
The discovery could not have been made without the generosity of Australians who donated their eyes to the Lions NSW Eye Bank so providing the critical evidence that what was seen in mouse experiments was also causing the cell death in humans with this form of AMD, says Professor Jan Provis of The Vision Centre and Australian National University.
"We've known for some time that cell death is the cause of dry AMD. What was not clear until now was what the mechanism was that caused the cells to die," Prof. Provis says. (Dry AMD is caused by the progressive atrophy of the macula and is the commonest form of the disease. Wet AMD is less common and is caused by overgrowth of blood vessels in the macula.)
"As its name suggests, the role of DICER-1 is to dice and slice products, to control gene expression inside cells. It's part of the cell's house-keeping mechanism.
"In particular DICER-1 removes a part of the "Ënon-coding' RNA called Alu, which if allowed to accumulate in the vision cells will stress and kill them.
"To complicate the picture, it appears the Alu also causes the decline in DICER-1 "“ so it's a circular effect. But we still do not understand what sets this cell death mechanism off."
However understanding what causes cell death takes scientists a step closer to finding a possible cure where none now exists. The study also explores ways of inhibiting the Alu to prevent depletion of DICER, and rescue the affected cells. An alternative strategy is to use gene therapy that would boost the amount of DICER-1, she says.
The discovery may also shed new light on cancer research in general, as DICER-1 is also implicated in the processes leading to various forms of cancer.
Prof Provis says a larger question is why this mechanism attacks the macula of the human eye specifically.
"My view is that the macula is a very delicate structure, so specialized to see fine details that it is balanced, in a functional sense, "Ëon a knife-edge'. A small factor like a loss of oxygen can tip it over "“ trigger a cascade of events that result in degeneration. This means that disease-causing factors may tend to show up in the macula first. If we can understand what's happening in the eye, it may offer us insights into what causes a range of diseases in other parts of the body."
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