Studying a mouse model of age-related macular degeneration, the leading cause of blindness in older Americans, scientists at Washington University School of Medicine in St. Louis have found age is key in determining whether damaging blood vessels will form beneath the retina and contribute to vision loss.
The scientists discovered that specific immune cells called macrophages play a role in the disease process in older mice by failing to block the development of abnormal, leaky blood vessels behind the retina. But in younger mice, macrophages typically prevent abnormal blood vessel formation.
The scientists believe better understanding of how macrophages work may provide potential targets for therapies to slow or even reverse vision loss. The findings are reported in the November issue of the Journal of Clinical Investigation.
Age-related macular degeneration is the leading cause of blindness in the United States in people over the age of 50. It accounts for more than 40 percent of blindness among the elderly in nursing homes, and as baby boomers get older, the problem is expected to grow, with at least 8 million cases predicted by the year 2020.
Whether the macrophages will block or encourage the growth of damaging blood vessels is related to the subtype of macrophage according to principal investigator Rajendra S. Apte, M.D., Ph.D., assistant professor of ophthalmology and visual sciences.
"There are two basic types of macrophages — known as M1 and M2 — and in the older mice, there was a preponderance of cells with the M2 signature," he says. "These M2 cells promoted abnormal blood vessel growth in the eyes of older mice. In younger mice, most macrophages had the M1 signature, and those cells inhibited the development of defective blood vessels."
Apte says it appears the population of macrophages drifts from the M1 type to M2 cells because of an increase in the levels of an immune system molecule called interleukin-10 (IL-10) in the eye as the mice get older. In a previous study, his team had found that high levels of IL-10 interfere with macrophages' ability to regulate blood vessel growth. As mice got older, the animals made more IL-10, and this caused more macrophages to become the M2 type.
"The older mice had much higher levels of IL-10," Apte explains. "That suggests IL-10 may be driving this process because higher IL-10 levels are associated with more M2 macrophages that cannot regulate blood vessel growth, and lack of IL-10, as in genetic knockout mice, leads to a preponderance of M1 macrophages."
The blood vessels that form in age-related macular degeneration are not like the mature vessels found in most of the body. Vessels associated with the disease don't have normal, tight junctions, but rather leak and bleed. They also tend to be located beneath the macula, the center of the retina, and when they bleed, the result is loss of vision.