Scientists at Schepens Eye Research Institute have discovered that a particular immune cell contributes to the growth of new lymph vessels, which aid in healing. This cell, known as a macrophage, is called in by the body during the wound healing process.
The discovery of this new role for the macrophage, published in the September 2005 Journal of Clinical Investigation, may ultimately inspire innovative treatments for blinding eye disease, as well as for other diseases, such as cancer, that rely on the lymph vessels to spread abnormal cells throughout the body.
"This is a very significant finding," according to Joan Stein-Streilein, PhD, and Patricia A. D'Amore, PhD, senior authors of the study, Senior Scientists at SERI and members of the Departments of Medicine and Ophthalmology at Harvard Medical School, respectively. "It unlocks a whole new dimension in our understanding of these important cells."
The body uses lymph vessels to bring immune cells to an injured organ to carry away debris and fluid to aid healing. Lymph vessels can play a different kind of role in cancer, offering tumor cells a pathway for spreading to other body parts, in a process known as metastasis.
Macrophages are large white blood cells called in during wound healing to ingest foreign invaders such as bacteria. They can also present pieces of those intruders to the immune system to jump-start the immune response. Produced in the bone marrow, they can be found in almost all tissues of the body. Unlike many other parts of the body, the clear outer layer of the eye, known as the cornea, does not normally have lymph vessels, except when injury causes lymph vessels to sprout from the edge of the cornea to help heal the wound.
Dr. Kazuichi Maruyama, a post-doctoral fellow in D'Amore's and Stein-Streilein's laboratories at SERI, began to suspect a new connection between macrophages and lymph vessels while studying corneal transplants in mice. He became aware of lymph vessels that seemed to be forming "in place," away from those produced at the edge of the cornea. He also noticed that these lymph vessels disappeared after the wounds were healed. Because the cell structure of the new vessels resembled that of macrophages, he began to believe there might be a relationship.
In the JCI study, he tested this idea by placing sutures in the corneas of two groups of mice to create injuries that would induce a healing response. Then he gave one group of mice a drug to cause macrophages to commit suicide. When he examined the eyes of both groups, he found those given the drug did not grow as many lymph vessels as the control group without the drug.
The implications of this link between macrophages and lymph vessels are far-reaching, according to Stein-Streilein, D'Amore, and Maruyama.
D'Amore and Stein-Streilein believe that harnessing this newly found ability of the macrophages could lead to the creation of new drugs or therapies for eye disease. For instance, inducing new "temporary" lymph vessels in retinas could aid in treating diabetic retinopathy by removing fluids leaking from abnormal blood vessels. It is this leaking fluid, characteristic of diabetic retinopathy that can permanently damage the retina and vision.
Maruyama speculates that the involvement of macrophages in forming lymph vessels may be universal and may also be involved in spreading cancer. If that were the case, blocking macrophages from helping to grow lymph vessels could inhibit the spread of tumors.
The team is now researching the same process in skin wounds and cancer.