Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

New discovery may help transplants survive

05.08.2004


Blocking growth factor stops rejection process



For the first time scientists have found that a growth factor called vascular endothelial growth factor receptor-3 (VEGFR-3), known to cause the growth of lymphatic vessels in the body, controls how immune cells traffic (move) within the eye and also stimulates the immune system to reject corneal transplants--the most common type of transplantation performed. The researchers from the Schepens Eye Research Institute and the Massachusetts Eye and Ear Infirmary, both affiliates of Harvard Medical School, have also found that when this growth factor is blocked, corneal transplants survive. The study, published in the August issue of Nature Medicine, is the first to make a link between VEGEFR-3 and the body’s immune response, and may hold significant promise not only for new treatments to prevent transplant rejection but also for diseases such as cancer that may proliferate because of VEGF-3.

"What we have discovered is a previously unknown connection or ’pathway’ that stimulates the immune response in the eye and in other parts of the body," says Reza Dana, MD, MPH, a Senior Scientist at the Schepens Eye Research Institute, an Associate Professor and corneal specialist at the Massachusetts Eye and Ear Infirmary and Harvard Medical School, and the senior author of the study.


Each year, nearly 40 thousand Americans receive corneal transplants to replace injured or diseased corneas. Approximately 90 percent of corneal transplants are successful because the eye is intrinsically less likely to reject transplanted material than other parts of the body. However, to suppress rejection of corneal transplants, patients need to use steroid drops – which can cause glaucoma, cataract development, and infection -- for years. Even then, many corneal transplants fail, and their failure can cause devastating vision loss. If transplants are placed in eyes suffering from inflammation (caused by a full-blown immune response to the original injury or disease), rejection rates go well over 50 percent, regardless of the therapy employed.

"We are trying to understand what is happening at the molecular level so that we can arrest this process," says Dana, who has devoted much of his research to finding the mechanisms that trigger immune responses, and, in the case of corneal transplants, the "unwanted" immune response that causes corneal transplant rejection.

VEGFR-3’s role in activating the immune response in the cornea is the most recent in a series of discoveries by Dana and his research team in their exploration of the immune response to corneal transplants.

In the normal immune response, cells known as antigen-presenting cells (APCs) are activated when they detect the presence of proteins (also known as "antigens") from foreign intruders such as bacteria, or, in the case of transplantation, proteins from other people. The job of the APCs -- which exist in all body tissues -- is to notify the immune system of the foreign tissue, pick up that tissue and then travel through vessels known as lymphatics to the lymph nodes where they can activate immunity. In the lymph nodes, APCs present the foreign protein to T Cells, which then custom design an immune attack to destroy the invader.

In previous work, Dana and his team found that removing the lymph nodes that drain the eyes prevented rejection of transplants that were vulnerable. They also found that VEGFR-3, known to cause the growth of lymphatic vessels, was expressed on the APCs and new lymphatic vessels were present in the corneas that were inflamed (or under immune attack.)

In the August Nature Medicine study, Dana and his colleagues hypothesized that when a cornea becomes inflamed, VEGFR-3 becomes activated on the antigen-presenting cells. They also believed that VEGFR-3 then triggered the APCs to move into the lymphatic vessels en route to the lymph nodes to make contact with the T-cells.

Using in-the-dish (in vitro) and living mice (in vivo), the team was able to show that VEGFR-3 was responsible for mobilizing APCs to move into the lymphatic system. Next, the research team blocked VEGFR-3 in mice using a specific protein (immunoglobulin) known to impede its function. When the VEGFR-3 was blocked, the APCs were also prevented from entering the lymphatic system, and the immune response was arrested. "We had never seen this connection before," says Dana. He added that while this connection was determined for the eye, it may well operate in other tissues as well.

While Dana says it is not yet clear exactly how this discovery will translate to the clinical setting, he believes continued study of this new pathway has potential for improving transplantation in the eye and potentially other parts of the body.

And, it could be a new piece of the cancer puzzle. "It has been shown that antigen presenting cells around tumors also express VEGFR-3 and we already know that access to lymphatics and lymph nodes is the way cancers spread through the body," he says.

"The findings of Dr. Dana and his colleagues provide new insights into transplant immunology and biology which go well beyond the eye, and offer new therapeutic approaches in organ transplantation and cancer treatment. Dr. Dana is clearly one of the outstanding physician scientists in our department," says Joan W. Miller, MD, Chief and Chair of Ophthalmology at Massachusetts Eye and Ear Infirmary and Harvard Medical School.

Patti Jacobs | EurekAlert!
Further information:
http://www.eri.harvard.edu

More articles from Health and Medicine:

nachricht Using fragment-based approaches to discover new antibiotics
21.06.2018 | SLAS (Society for Laboratory Automation and Screening)

nachricht Scientists learn more about how gene linked to autism affects brain
19.06.2018 | Cincinnati Children's Hospital Medical Center

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

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

Im Focus: Temperature-controlled fiber-optic light source with liquid core

In a recent publication in the renowned journal Optica, scientists of Leibniz-Institute of Photonic Technology (Leibniz IPHT) in Jena showed that they can accurately control the optical properties of liquid-core fiber lasers and therefore their spectral band width by temperature and pressure tuning.

Already last year, the researchers provided experimental proof of a new dynamic of hybrid solitons– temporally and spectrally stationary light waves resulting...

Im Focus: Overdosing on Calcium

Nano crystals impact stem cell fate during bone formation

Scientists from the University of Freiburg and the University of Basel identified a master regulator for bone regeneration. Prasad Shastri, Professor of...

Im Focus: AchemAsia 2019 will take place in Shanghai

Moving into its fourth decade, AchemAsia is setting out for new horizons: The International Expo and Innovation Forum for Sustainable Chemical Production will take place from 21-23 May 2019 in Shanghai, China. With an updated event profile, the eleventh edition focusses on topics that are especially relevant for the Chinese process industry, putting a strong emphasis on sustainability and innovation.

Founded in 1989 as a spin-off of ACHEMA to cater to the needs of China’s then developing industry, AchemAsia has since grown into a platform where the latest...

Im Focus: First real-time test of Li-Fi utilization for the industrial Internet of Things

The BMBF-funded OWICELLS project was successfully completed with a final presentation at the BMW plant in Munich. The presentation demonstrated a Li-Fi communication with a mobile robot, while the robot carried out usual production processes (welding, moving and testing parts) in a 5x5m² production cell. The robust, optical wireless transmission is based on spatial diversity; in other words, data is sent and received simultaneously by several LEDs and several photodiodes. The system can transmit data at more than 100 Mbit/s and five milliseconds latency.

Modern production technologies in the automobile industry must become more flexible in order to fulfil individual customer requirements.

Im Focus: Sharp images with flexible fibers

An international team of scientists has discovered a new way to transfer image information through multimodal fibers with almost no distortion - even if the fiber is bent. The results of the study, to which scientist from the Leibniz-Institute of Photonic Technology Jena (Leibniz IPHT) contributed, were published on 6thJune in the highly-cited journal Physical Review Letters.

Endoscopes allow doctors to see into a patient’s body like through a keyhole. Typically, the images are transmitted via a bundle of several hundreds of optical...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Munich conference on asteroid detection, tracking and defense

13.06.2018 | Event News

2nd International Baltic Earth Conference in Denmark: “The Baltic Sea region in Transition”

08.06.2018 | Event News

ISEKI_Food 2018: Conference with Holistic View of Food Production

05.06.2018 | Event News

 
Latest News

Graphene assembled film shows higher thermal conductivity than graphite film

22.06.2018 | Materials Sciences

Fast rising bedrock below West Antarctica reveals an extremely fluid Earth mantle

22.06.2018 | Earth Sciences

Zebrafish's near 360 degree UV-vision knocks stripes off Google Street View

22.06.2018 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>