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

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."


Contact: Morwenna Grills
University of Manchester

Related biology news :

1. Explosive breakthrough in research on molecular recognition
2. Mainz scientists confirm original tetrahedral model of the molecular structure of water
3. FASEB SRC announces: Molecular Mechanisms & Physiological Consequences of Protein Aggregation
4. FASEB SRC announces conference registration open for: Ciliate Molecular Biology
5. Elsevier launches new open access journal: Molecular Metabolism
6. Virginia Tech computer scientists develop new way to study molecular networks
7. Molecular forces are key to proper cell division
8. La Jolla Institute identifies molecular switch enabling immune cells to better fight disease
9. Molecular 2-way radio directs nerve cell branching and connectivity
10. Scientists pinpoint molecular signals that make some women prone to miscarriage
11. Webcast alert: Molecular Medicine Institute to give new hope to pediatric patients
Post Your Comments:
(Date:11/9/2015)...  Synaptics Inc. (NASDAQ: SYNA ), the leading ... into the automotive market with a comprehensive and dedicated ... consumer electronics human interface innovation. Synaptics, industry-leading touch controllers, ... automotive industry and will be implemented in numerous locations ... , Japan , and ...
(Date:10/29/2015)... 29, 2015  The J. Craig Venter Institute (JCVI) ... Synthesis and Biosecurity: Lessons Learned and Options for the ... and Human Services guidance for synthetic biology providers has ... --> --> Synthetic biology ... potential to pose unique biosecurity threats. It now is ...
(Date:10/29/2015)... NXTD ) ("NXT-ID" or ... the growing mobile commerce market and creator of ... leading marketplace to discover and buy innovative technology ... on StackSocial for this holiday season.   ... a biometric authentication company focused on the growing ...
Breaking Biology News(10 mins):
(Date:11/24/2015)... SHPG ) announced today that Jeff Poulton , Chief ... Annual Healthcare Conference in New York City , ... p.m. GMT). --> SHPG ) announced today that ... Jaffray 27 th Annual Healthcare Conference in New ... 8:30 a.m. EST (1:30 p.m. GMT). --> Shire plc ...
(Date:11/24/2015)...  Tikcro Technologies Ltd. (OTCQB: TIKRF) today announced that its Annual General ... a.m. Israel time, at the law offices of ... 36 th Floor, Tel Aviv, Israel . ... Izhak Tamir to the Board of Directors; , election ... , approval of an amendment to certain terms of options granted to ...
(Date:11/24/2015)...  Twist Bioscience, a company focused on synthetic ... Bioscience chief executive officer, will present at the ... 2015 at 3:10 p.m. Eastern Time at The Lotte New ... --> --> About Twist ... on Twitter. Sign up to follow our Twitter ...
(Date:11/24/2015)... ... November 24, 2015 , ... InSphero AG, the leading ... culture models, has promoted Melanie Aregger to serve as Chief Operating Officer. ... on the management team and was promoted to Head of InSphero Diagnostics ...
Breaking Biology Technology: