June 10, 2011

Scientists Find How Rogue Cells ‘Eat Our Eyes’

Vision scientists have identified a key player in macular degeneration (MD), raising hope for a treatment for the currently incurable blinding disease.

The studies reveal how light-damaged eyes invoke an out-of-control immune response, resulting in white blood cells invading the retina and leaving behind proteins that kill the light sensitive vision cells.

This type of immune attack is seen in macular degeneration, which accounts for half of the vision loss cases in Australia, costing the nation $2.6 billion a year. The research team from The Vision Centre and The Australian National University says that their results show how this process of immune attack occurs, and how it can be controlled.

"When the cells in our eyes are damaged, the immune response kicks in and sends macrophages "“ white blood cells that "Ëœeat' invading or dead cells "“ to clean up the mess," say the researchers. "If the immune system is not properly regulated, the invading cells linger and call in even more macrophages "“ literally, "Ëœbig eaters'.

"Our study shows that the macrophages deposit a complex of proteins on retinal cells, which then kills them. The macrophages clean up the remains, and if the immune system doesn't control the process, the light-sensitive cells die and get eaten away by the macrophages."

In macular degeneration macrophages attack vision cells in the fovea "“ a "Ëœpit' at the back of the eye, which is the critical region for detailed vision, enabling us to do things like read, recognise faces and see small detail.

The researchers say that previous research, mostly done in Australia, showed that these "Ëœrogue' macrophages are involved in macular degeneration, but it wasn't clear what was driving them or how they contributed to degeneration.

By studying light-damaged eyes in rats, the Vision Centre team found that when the retina is damaged by bright light, it increases its production of a molecule known as Ccl2, which attracts macrophages into the eye. The team has shown that peak levels of Ccl2 coincide with the highest death rates of vision cells.

The macrophages then bring in another molecule, known as C3. This causes the formation of a complex of molecules called a "Ëœmembrane attack complex', which coats the light-sensitive cells, causing them to die. The macrophages then eat up the remains.

"We knew that the membrane attack complex is present in macular degeneration, but we didn't know how it got there. Now we know that it is started by macrophages that are attracted by Ccl2," says Professor Jan Provis, who heads the team.

"It was discovered in 2005 that many sufferers of macular degeneration have a defect in a factor that breaks down C3, but that research did not show how the C3 gets into the retina. Our study shows that it is brought in by the macrophages, attracted by Ccl2."

Identifying Ccl2 leads to a potential path for treating the dry form of macular degeneration: "Pinning down Ccl2 gives us a target "“ we can start looking for ways to block Ccl2, and so prevent the attraction of macrophages into the retina and the accumulation of C3."

The team is currently exploring whether shining a soft infra-red light on light-damaged eyes can inhibit Ccl2 growth. If this works, it will lead to a cheap and non-intrusive way of slowing down macular degeneration. The early results are promising, they say.

The research team has published two journal articles that are related to the topic in Investigative Ophthalmology and Visual Science. The published papers are:

"Early focal expression of the chemokine Ccl2 by Mller cells during exposure to damage-inducing bright continuous light" by Matt Rutar, Riccardo Natoli, Krisztina Valter and Jan M. Provis, available at http://bit.ly/in4XIr

"Analysis of complement expression in light-induced retinal degeneration: Synthesis and deposition of C3 by microglia/macrophages is associated with focal photoreceptor degeneration" by Matt Rutar, Riccardo Natoli, Peter Kozulin, Krisztina Valter, Paul Gatenby and Jan M. Provis, available at http://bit.ly/lxuVgs

The team presented their findings at The Association for Research in Vision and Ophthalmology (ARVO) conference in May 2011.

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


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