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New discovery may help transplants survive

ection 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) a
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Contact: Patti Jacobs
pjacobs12@comcast.net
627-872-0364
Schepens Eye Research Institute
4-Aug-2004


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