December 7, 2010

Macular Degeneration: Immune System Gone Wild

Scientists at The Vision Centre have found new evidence that the common blinding disease macular degeneration (MD) may result from poorly regulated immune responses similar to those linked to Alzheimer's disease or cerebral haemorrhages.

The leading cause of vision loss and blindness in Australia, macular degeneration often occurs as a result of the immune system going into overdrive and killing more vision cells than it should, according to new evidence found by PhD student Matt Rutar from the ARC Centre of Excellence for Vision Science.

"Our results suggest that the response works as a vicious cycle, with white blood cells the major culprit," Matt says. "Upon inflammation or damage to the eyes, the immune system kicks in and white blood cells, particularly macrophages, are recruited to clean up the debris or dead cells."

"Under healthy conditions, the white blood cells finish their task and leave the macula. However, in cases of MD, the macrophages call in other inflammatory proteins and combine with them. This then triggers a fresh cycle in which they attack healthy vision cells."

The finding was made using albino rats with a low tolerance for excessive light, enabling the researchers to study the immune process in action.

"The immune response can be provoked by signals such as those from drusen "“ white deposits in the inner layer of the eye "“ or vision cells that have died naturally or as a result of inflammation. These become cell debris which triggers the immune reaction."

"Macular degeneration is a long term and very gradual process, from years of accumulated damage," he says. "It is similar to the kind of central nervous system damage that we see in cases of Alzheimer's disease and cerebral haemorrhage. Our photoreceptors die regularly "“ it is a normal occurrence, and we always have cell debris in our eyes. The problem is when the immune system starts to get out of control, which happens as you age - and that is why age is one of the biggest risk factors in MD."

"Apart from losing vision cells as we age, our immune system can become poorly regulated, to the point where it causes further damage to the vision cells."

The best way to prevent MD at present, he says, is to prevent any unnecessary inflammation of the eyes.

"The best advice at the moment is:
"¢ wear sunglasses whenever we go out into sunny conditions or are exposed to bright light
"¢ minimise our long term exposure to excessive light
"¢ maintain an omega three-rich diet to minimise free radicals that can harm our bodies
"¢ exercise regularly to keep a normal level blood pressure and
"¢ avoid activities that weaken our immune system, such as smoking."

"This research has given us broad snapshots of what goes on within the vision processes of the eye itself and allowed us to understand how age-related blindness develops. The next step is to track the inflammatory process in detail, with a view to interrupting it."

Matt was awarded the prize for best student presentation at the annual Research School of Biology 2010 student conference for his presentation of this research.

The research team has published two journal articles that are related to the topic and is about to submit a third. The published papers are:

Rutar M, Provis JM, Valter K. Brief exposure to damaging light causes focal recruitment of macrophages, and long-term destabilization of photoreceptors in the albino rat retina. Current Eye Research 2010; 35:631-643.

Rutar M, Natoli R, Valter K, Provis JM. Early focal expression of the chemokine Ccl2 by Mller cells during exposure to damage-inducing bright continuous light. Investigative Ophthalmology and Vision Science 2010; In press.

The Vision Centre is funded by the Australian Research Council as the ARC Centre of Excellence in Vision Science.


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