Study Explains How Smoking Raises Risk of Macular Degeneration

DURHAM, N.C. - Cigarette smoke and its component tar trigger the formation of deposits and thickening in the retina that cause age-related macular degeneration, Duke University Medical Center researchers have found. In experiments with mice, they also discovered heavy exposure to secondhand smoke produces similar changes.
The study is the first to examine the mechanism by which smoking causes macular degeneration, the leading cause of blindness in the elderly, the researchers said. Several large epidemiologic studies have shown that smoking more than doubles the risk of age-related macular degeneration (AMD), said study author Ivan Suñer, M.D., associate professor of ophthalmology at the Duke Eye Center. But until now, no one had explored how cigarette smoke generates biological changes in the eye that lead to vision loss and, in some cases, blindness.
"Understanding the molecular mechanism that causes these changes may lead to models that allow us to understand how macular degeneration is occurring. By understanding the biology, we may also be able to develop therapies to protect nonsmokers as well as smokers," Suñer said.
The results appear in the February 2006 issue of Investigative Ophthalmology & Visual Science. The study was funded by the National Eye Institute, the Flight Attendants' Medical Research Institute and a Veterans Affairs Merit Review Award.
AMD is a progressive disease that damages the retina, the thin layer of nervous tissue that lines the inside of the eye. The retina receives images from the eye's lens and transmits them to the brain. In AMD, the primary site of damage is the central retina, an area called the macula. The macula handles fine detail vision, such as driving and reading.
There are two types of AMD - the milder "dry" form and the more severe "wet" form. In dry AMD, the degeneration of the macula occurs slowly and progressively over months or years. There is no cure, but studies have shown certain vitamins can slow development of the disease in some people. Only 10 percent of people with dry AMD develop wet AMD, in which abnormal blood vessels leak blood and fluid under the macula, causing rapid vision loss and damage.
The research team examined the relationship between dry AMD and cigarette smoke, including one of its components, hydroquinone - the main ingredient of tar. Typically, scientists study dry AMD in mice by exposing a specific mouse strain prone to the disorder to ultraviolet (UV) light and feeding the animals a high-fat diet.
"These oxidants are thought to initiate the changes that result in dry AMD," Suñer said. The researchers found that the combination of the three oxidant "hits" smoke, UV light and a high-fat diet exacerbated the effects of smoking on macular degeneration, Suñer said. The Duke team also exposed the animals to cigarette smoke instead of ultraviolet light and found the mice developed retinal changes indicative of early AMD.
The researchers also tested the effects of smoke on mice that were not fed a high-fat diet or exposed to UV light. These mice developed deposits under the retina, signs of early dry AMD. The researchers found similar changes in mice subjected to heavy secondhand smoke.
"Our study shows that cigarette smoking alone can cause development of macular degeneration changes. Heavy exposure to secondhand smoke can also cause these changes," Suñer concluded.
Because the byproducts of cigarette smoke accumulate in the lungs and circulate in the body, the researchers also investigated how ingesting one of the potent oxidants in tar would affect mice. They fed the animals hydroquinone, a benzene derivative that is a major component of cigarette tar. After 4.5 months, the mice had developed the deposits and thickening of early dry AMD whether they ate a low-fat or a high-fat diet. They were not exposed to UV light.
"Tar is just one potential oxidant in cigarette smoke; there are other chemicals like nicotine, carbon monoxide and carbon dioxide. However, this reinforces the finding that antioxidants and smoking cessation are helpful in protection for dry macular degeneration," Suñer said. "The interesting thing about hydroquinone is that it is in pollution in the atmosphere, and we are seeing more and more macular degeneration developing in areas with high pollution rates," he said.
"Our group also previously demonstrated that nicotine makes active wet macular degeneration worse. This is important because this implies that patients with active wet AMD should not smoke or use nicotine replacement therapies," Suñer added.
Co-authors include Scott Cousins of the Duke Eye Center, and Diego Espinosa-Heidmann, Paola Catanuto, Eleut Hernandez and Maria Marin-Castano of the Bascom Palmer Eye Institute at the University of Miami School of Medicine, Miami, Fla.