Biologists at UCSB recently published research that identified a gene responsible for the most common form of irreversible elderly blindness in developed countries.

The blinding disease is known as age-related macular degeneration (AMD), and affects about 50 million people worldwide. The disease causes a loss of central vision due to a degradation of the macula, the part of the eye’s retina responsible for creating a clear image. Don Anderson, director of the UCSB Center for the Study of Macular Degeneration and Lincoln Johnson, associate director of the center, took part in a collaborative study that involved seven universities and research institutes in the United States and Europe. The study found that AMD is caused by inflammation in the eye, and the lack of a bodily substance called factor H may be responsible for this harmful inflammation. The study was published in the Proceedings of the National Academy of Sciences in April.

Among the collaborators that participated in this study, the two UCSB researchers performed the physical lab work that involved comparing chemicals found in eyes from people with AMD and those with healthy eyes. Anderson said this research marks a very important step in studying AMD that may lead to possible treatments.

“I think this study, along with several others, are regarded as a major advance,” Anderson said. “Most of the experts in the field, including the director of the national eye institute and almost everyone that’s quoted on the Internet, have recognized that that’s the case. It’s a breakthrough. I think it’s fair to say that.”

Anderson and Johnson began work on this course of research about six years ago in an effort to learn more about AMD by determining what chemicals are abnormally present – or absent – in patients with the disease. They found that AMD might be caused or aggravated by a part of the body’s immune system, which is usually responsible for fighting off germs.

“[The immune system involvement] is something that we basically discovered over the past several years in looking at the molecular attributes of the disease – figuring out what molecules are present in the eyes of people with macular degeneration that either shouldn’t be there or are there in abnormal amounts or are in the wrong place,” Johnson said. “And by that analysis we came up with a list of molecules that pointed us in the direction. It has all the earmarks of an inflammatory response.”

Inflammation is a sign that the body’s immune system is at work, dropping chemicals on a particular site to help destroy intruding organisms. When a splinter pierces the skin, the surrounding flesh swells with immune system chemicals to keep the area from getting infected. Johnson and Anderson found a similar process occurring in the eyes of people with AMD, but it appeared as if the immune system was attacking normal bodily cells instead of germs. To make matters worse, the pair discovered that this inflammation seems to be present chronically in AMD sufferers, slowly damaging the eye over time.

“It’s a low-level pounding over years and years and years that ultimately has a detrimental effect, and that’s maybe why these diseases show up late in life,” Johnson said. “The immune system is really quite complex, and it has several different arms, but the presence of inflammatory cells and molecules indicates that the immune system has been triggered.”

After having established a connection between the immune system and AMD, the two researchers began to investigate why the body would attack itself like this. They found that normal bodily cells have a coating that contains a chemical called factor H, which acts like an I.D. tag and instructs the immune system to ignore those cells. The branch of the immune system that reads these tags – known as the complement cascade – appears to be working well in people with AMD, but their cells’ tags seem to be defective.

“Here we have almost an immediate response of a system called the complement cascade, which is a product of evolution and it is designed to recognize molecules on the surface of bacteria and other particles that are present on most of those foreign [germs], but are absent on the [body’s] tissue,” Anderson said.

In healthy people, the immune system is able to recognize germs by their unfamiliar surface molecules, and bodily cells by their factor H coatings. In people with AMD, it appears the factor H is unreadable, and so the immune system thinks the bodily cells are germs and attacks them, Anderson said. This leads to inflammation and, over time, destruction of eye’s ability to see.

Johnson and Anderson also found that one particular gene is responsible for the non-functional factor H. If this bit of DNA could be repaired genetically, that would constitute one form of treatment, Anderson said.

“You can entertain the idea of replacing the bad factor H with good factor H, and that could be done in a variety of different ways,” Anderson said. “It’s conceivable you could use gene-replacement therapy to put a good copy of factor H into cells removed from a person’s liver.”

The liver is where the majority of the body’s factor H is made, so that would make it a good target for gene therapy, Anderson said. He also said factor H might possibly be introduced directly into the body.

“You could give an intravenous injection or a sustained delivery of factor H,” Anderson said. “You could remove all of the bad factor H and see if the system could compensate.”