Scientists at Schepens Eye Research Institute have discovered that aparticular immune cell contributes to the growth of new lymph vessels,which aid in healing. This cell, known as a macrophage, is called in bythe body during the wound healing process. The discovery of this newrole for the macrophage, published in the September 2005 Journal ofClinical Investigation, may ultimately inspire innovative treatmentsfor blinding eye disease, as well as for other diseases, such ascancer, that rely on the lymph vessels to spread abnormal cellsthroughout the body.
"This is a very significant finding," according to JoanStein-Streilein, PhD, and Patricia A. D'Amore, PhD, senior authors ofthe study, Senior Scientists at SERI and members of the Departments ofMedicine and Ophthalmology at Harvard Medical School, respectively. "Itunlocks a whole new dimension in our understanding of these importantcells."
The body uses lymph vessels to bring immune cells to an injured organto carry away debris and fluid to aid healing. Lymph vessels can play adifferent kind of role in cancer, offering tumor cells a pathway forspreading to other body parts, in a process known as metastasis.
Macrophages are large white blood cells called in during wound healingto ingest foreign invaders such as bacteria. They can also presentpieces of those intruders to the immune system to jump-start the immuneresponse. Produced in the bone marrow, they can be found in almost alltissues of the body. Unlike many other parts of the body, the clearouter layer of the eye, known as the cornea, does not normally havelymph vessels, except when injury causes lymph vessels to sprout fromthe edge of the cornea to help heal the wound.
Dr. Kazuichi Maruyama, a post-doctoral fellow in D'Amore's andStein-Streilein's laboratories at SERI, began to suspect a newconnection between macrophages and lymph vessels while studying cornealtransplants in mice. He became aware of lymph vessels that seemed to beforming "in place," away from those produced at the edge of the cornea.He also noticed that these lymph vessels disappeared after the woundswere healed. Because the cell structure of the new vessels resembledthat of macrophages, he began to believe there might be a relationship.
In the JCI study, he tested this idea by placing sutures in the corneasof two groups of mice to create injuries that would induce a healingresponse. Then he gave one group of mice a drug to cause macrophages tocommit suicide. When he examined the eyes of both groups, he foundthose given the drug did not grow as many lymph vessels as the controlgroup without the drug.
The implications of this link between macrophages and lymph vessels arefar-reaching, according to Stein-Streilein, D'Amore, and Maruyama.
D'Amore and Stein-Streilein believe that harnessing this newly foundability of the macrophages could lead to the creation of new drugs ortherapies for eye disease. For instance, inducing new "temporary" lymphvessels in retinas could aid in treating diabetic retinopathy byremoving fluids leaking from abnormal blood vessels. It is this leakingfluid, characteristic of diabetic retinopathy that can permanentlydamage the retina and vision.
Maruyama speculates that the involvement of macrophages in forminglymph vessels may be universal and may also be involved in spreadingcancer. If that were the case, blocking macrophages from helping togrow lymph vessels could inhibit the spread of tumors.
The team is now researching the same process in skin wounds and cancer.
SchepensEye Research Institute, and affiliate of Harvard Medical School, is thelargest independent eye research institute in the world.
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