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Study Explains How Smoking Raises Risk of Macular Degeneration

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Duke Health News 919-660-1306

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
University 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.

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