Age-related macular degeneration (AMD) is the leading cause of vision loss among older adults, and affects more than 1.75 million people in the U.S. It begins with a dark spot on the macula, which is the central part of the retina, and leads to a gradual loss of central vision that eventually progresses to full blindness.
Researchers at the University of California (UC), San Diego, have revealed insights into how the innate immune system responds to oxidative stress, caused by our bodies reacting to the oxygen we breath and the energy produced by our cells. Oxidative stress affects the body’s normal aging process and is considered a cause of many health conditions such as Alzheimer’s disease, atherosclerosis, myocardial infarction, and AMD. The innate immune system, also known as the non-specific immune system, provides immediate defense against infection before the adaptive immune system kicks in.
The UC San Diego researchers, led by Christoph J. Binder, assistant adjunct professor of medicine, have identified a key protein in the eye that binds to a molecule generated by oxidative stress. The molecule blocks any immune response by the body beyond the innate immune system. The scientists believe that this could be exploited to prevent and treat AMD and other chronic inflammatory diseases.
Scott LaFee of the UC San Diego public relations department explains further,
Specifically, Binder, Joseph L. Witztum, professor of medicine at UC San Diego, and colleagues in Austria, Germany, England and Maryland discovered that when lipids (fats) in cell membranes degrade through oxidative stress, they produce a number of reactive products, including a compound called malondialdehyde (MDA), which in turn modifies other molecules to create novel oxidation-specific epitopes, the part of antigens that draws the attention and inflammatory response of the innate immune system.
The researchers noted, in particular, that MDA attracted an immune system protein called complement factor H (CFH), which bound to it, effectively blocking the uptake of MDA-modified proteins by macrophages, a type of white blood cell charged with killing and eliminating foreign invaders and substances. In in-vivo experiments, the researchers reported that CFH neutralized the inflammatory effects of MDA in mice retinas, limiting the inflammatory response associated with AMD and other chronic diseases.
At UC Davis, another campus of the University of California school system, researchers have been awarded a three-year, $1.8 million grant from the National Eye Institute (NEI), part of the National Institutes of Health, to study cellular changes related to AMD. Researchers will study how retinal pigment epithelium (RPE), a protective layer of cells outside the retina, is affected by epigenetics, or “changes that alter gene expression while leaving the original genome sequence intact.”
The project is one of the first to be funded by the NEI to explore the effects of epigenetics on eye disease. Larry Hjelmeland, UC Davis professor of ophthalmology with the UC Davis Eye Center and one of the principal researchers for the project, said, “Looking at aging as an epigenetic phenomenon clearly represents a big step forward for the study of AMD.”
Hjelmeland continued, “This new research direction could lead to novel ways to prevent and manage AMD and perhaps a cure. We want to bring new and better options to those who are coping with this disease.”