Velcro Therapy: Branching polymer wards off scarring after eye surgery

Glaucoma affects more than 3 million Americans and is the second-leading cause of blindness in the United States. Surgery can treat the disease, but the success rate is low and patients often require a second operation. Now, biomedical researchers have developed a therapy that could dramatically improve the procedure’s outcome.

The disease is marked by a buildup of fluid inside the eye, which exerts pressure on the optic nerve and eventually causes blindness. That pressure builds up when ducts surrounding the iris that normally drain excess fluid get blocked. Doctors treat the disease by surgically inserting an artificial tube to drain the fluid and relieve the pressure.

However, scar tissue forms and blocks the newly inserted tube in roughly one-third of all patients, rendering the treatment ineffective, says Sunil Shaunak at Imperial College London. Although doctors can reduce the scarring with medications, these drugs lead to other complications.

With the goal of preventing scar tissue formation and reducing the need for drugs, Shaunak and his colleagues set out to commandeer the immune system for the job. To do this, the researchers turned to polymers called dendrimers, which are about the size of proteins.

Each dendrimer consists of many polymer chains that branch out in all directions from a core. To the outer tips of these chains, the researchers added specific sugar molecules known to bind to receptors on, and thus to inhibit, immune cells involved in the inflammation that results in scarring. The sugars bound to the dendrimer in such a way that several of them would stick to each receptor, much as Velcro sticks to fabric, says Shaunak.

When the researchers injected a solution containing the dendrimers into the eyes of rabbits that had undergone glaucoma surgery, subsequent scarring was all but stopped and the success rate of the surgery shot up from 30 percent to 80 percent.

“We were absolutely stunned by the results,” says Shaunak. He and his colleagues describe the findings in the August Nature Biotechnology.

“This is a great piece of work,” says Donald Tomalia at Dendritic NanoTechnologies in Mount Pleasant, Mich. Tomalia suspects that this strategy could not only be applied to other types of surgery but that it could also engender therapies for inflammatory diseases such as rheumatoid arthritis. The inflammation-causing cells in those conditions bear the same kinds of receptors that the cells involved in scar formation carry.

Mark Grinstaff of Boston University is particularly encouraged by the results. Although dendrimers were developed in the 1980s, only recently have researchers successfully tested them in animals and shown their potential for medical applications. For instance, Grinstaff and his colleagues are developing dendrimer-based wound-healing materials for treating corneal lacerations. Researchers at the University of Michigan in Ann Arbor recently engineered dendrimers that inhibit the influenza A virus in mice. And a dendrimer-based therapy that blocks the AIDS-causing virus HIV is already being tried in patients in Australia.

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