Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Molecular basis identified for tissue specific immune regulation in the eye and kidney

21.02.2013
Both AMD, which affects around 50 million people worldwide, and aHUS, a rare kidney disease that affects children, are associated with incorrectly controlled immune systems.

A protein called complement factor H (CFH) is responsible for regulating part of our immune system called the complement cascade. Genetic alterations in CFH have been shown to increase a person's risk of developing either AMD or aHUS, but rarely both. Why this is the case has never been explained until now.

Researchers from the Wellcome Trust Centre for Cell Matrix Research and the Ophthalmology and Vision Research Group in The University of Manchester's Institute of Human Development have been expanding on their previous work that demonstrated a single common genetic alteration in CFH prevents it from fully protecting the back of the human eye. The research teams of Professor Tony Day and Professor Paul Bishop found that a common genetically altered form of CFH associated with AMD couldn't bind properly to a layer under the retina called Bruch's membrane. Having a reduced amount of CFH in this part of the eye leads to low-level inflammation and tissue damage, eventually resulting in AMD.

However, this mutation that changes CFH function in the eye has no affect on the protein's ability to regulate the immune system in the kidney. A cluster of genetic mutations in a completely different part of CFH are associated with the kidney disease aHUS, but these have no affect on the eyes.

In their most recent study, which was funded by the Medical Research Council and published in the Journal of Immunology, the Manchester researchers have identified why these mutations in CFH result in diseases in very specific tissues. Professor Day explains: "For the first time we've been able to identify why these protein mutations are so tissue specific. We're hoping our discovery will open the door to the development of tissue specific treatments to help the millions of people diagnosed with AMD every year."

The research team looked at the two parts of CFH affected by the mutations. Both regions are capable of recognising host tissues, through interacting with sugars called glycosaminoglycans (GAGs). Successfully recognising these GAGs lets CFH build up a protective layer on the surface of our tissues that prevents our own immune system from attacking them.

It had always been believed that the region with mutations associated with aHUS was the most important for host recognition and for years people have been researching how to readdress immune dysregulation based on this belief. However, the recent discovery of a single common genetic alteration in the other part of CFH that is associated with eye disease raised the possibility that this previous opinion was not fully accurate.

The Manchester researchers compared the way the different regions of the protein interacted with eye tissue and kidney tissue. They discovered that the region of CFH that helps protect the kidney had no effect in the eye. Instead the other part of CFH, which is subject to the AMD-associated genetic alteration, was fundamentally important in protecting the eye, but this region did not contribute to the binding of CFH to kidney tissue.

Their findings show, for the first time, that the level of importance of the two regions of CFH changes depending on which tissue the protein finds itself. This specificity appears to be mediated by the presence of different populations of GAGs.

Dr Simon Clark says: "Our findings suggest that the particular structure within the eye and kidney tissue determines precisely how and where CFH will bind. It's as if the tissues have their own molecular postcodes."

He continues: "We're very pleased to be able to show why mutations in CFH are so tissue specific. This is important because if we're going to improve treatments for devastating diseases, such as AMD, we need to be able to develop tissue-specific therapies."

Professor Paul Bishop, theme lead at the Manchester Biomedical Research Centre and Consultant at the Manchester Royal Eye Hospital says: "The contribution of donor samples from Manchester Eye Bank was vital for this study. Without the tissue samples that had so generously been given for research by eye donors this research would have been impossible to do."

Morwenna Grills | EurekAlert!
Further information:
http://www.manchester.ac.uk

More articles from Life Sciences:

nachricht Warming ponds could accelerate climate change
21.02.2017 | University of Exeter

nachricht An alternative to opioids? Compound from marine snail is potent pain reliever
21.02.2017 | University of Utah

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Breakthrough with a chain of gold atoms

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

Im Focus: DNA repair: a new letter in the cell alphabet

Results reveal how discoveries may be hidden in scientific “blind spots”

Cells need to repair damaged DNA in our genes to prevent the development of cancer and other diseases. Our cells therefore activate and send “repair-proteins”...

Im Focus: Dresdner scientists print tomorrow’s world

The Fraunhofer IWS Dresden and Technische Universität Dresden inaugurated their jointly operated Center for Additive Manufacturing Dresden (AMCD) with a festive ceremony on February 7, 2017. Scientists from various disciplines perform research on materials, additive manufacturing processes and innovative technologies, which build up components in a layer by layer process. This technology opens up new horizons for component design and combinations of functions. For example during fabrication, electrical conductors and sensors are already able to be additively manufactured into components. They provide information about stress conditions of a product during operation.

The 3D-printing technology, or additive manufacturing as it is often called, has long made the step out of scientific research laboratories into industrial...

Im Focus: Mimicking nature's cellular architectures via 3-D printing

Research offers new level of control over the structure of 3-D printed materials

Nature does amazing things with limited design materials. Grass, for example, can support its own weight, resist strong wind loads, and recover after being...

Im Focus: Three Magnetic States for Each Hole

Nanometer-scale magnetic perforated grids could create new possibilities for computing. Together with international colleagues, scientists from the Helmholtz Zentrum Dresden-Rossendorf (HZDR) have shown how a cobalt grid can be reliably programmed at room temperature. In addition they discovered that for every hole ("antidot") three magnetic states can be configured. The results have been published in the journal "Scientific Reports".

Physicist Dr. Rantej Bali from the HZDR, together with scientists from Singapore and Australia, designed a special grid structure in a thin layer of cobalt in...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Booth and panel discussion – The Lindau Nobel Laureate Meetings at the AAAS 2017 Annual Meeting

13.02.2017 | Event News

Complex Loading versus Hidden Reserves

10.02.2017 | Event News

International Conference on Crystal Growth in Freiburg

09.02.2017 | Event News

 
Latest News

Impacts of mass coral die-off on Indian Ocean reefs revealed

21.02.2017 | Earth Sciences

Novel breast tomosynthesis technique reduces screening recall rate

21.02.2017 | Medical Engineering

Use your Voice – and Smart Homes will “LISTEN”

21.02.2017 | Trade Fair News

VideoLinks
B2B-VideoLinks
More VideoLinks >>>