Iron In Your Eyes

Link between iron overload and macular degeneration under study

http://esciencenews.com/articles/20...overload.and.macular.degeneration.under.study

Thursday, June 24, 2010 - 10:19 in Health & Medicine
Phil Jones Campus photographer
The most common – and under-diagnosed – genetic disease in humans just
may be a cause of the worst form of macular degeneration, Medical
College of Georgia researchers report. They are pursuing a link
between hemochromatosis, which results in iron overload, and the wet
form of macular degeneration, the leading cause of blindness in people
60 and older. They suspect that too much iron, known to wreak
cumulative havoc on the body's organs, hastens normal aging of the
eyes.

If they are correct, avoiding the most severe consequences of a
disease that robs the central vision could be as simple as donating
blood a couple times annually to reduce iron levels, said Dr. Vadivel
Ganapathy, chairman of the MCG School of Medicine Department of
Biochemistry and Molecular Biology.

A $1.5 million grant from the National Eye Institute is enabling the
MCG scientists to define the impact of hemochromatosis on the eye's
form and function. Support from MCG's Vision Discovery Institute is
enabling screening for its causative genetic mutation in the blood of
healthy individuals and those with macular degeneration.

"If this is a predisposing risk for macular degeneration, we have a
very useful tool for screening patients," said Dr. Julian Nussbaum, a
retinal specialist who chairs the School of Medicine's Department of
Ophthalmology and co-directs MCG's Vision Discovery Institute. "We can
give patients information right off the bat that may help them."

While linking iron overload to eye disease may seem odd, they have in
common the result of too much of a good thing. The eyes need light to
see and the body needs iron to deliver oxygen but the price of both is
increased oxidative stress, Ganapathy said. "You need oxygen and you
need iron to make this bad molecule," he said of oxygen radicals that
can destroy tissue down to the DNA.

Light alone takes a slow toll on the retina, which converts it into
electrical impulses sent to the brain via the optic nerve. This is
despite multiple built-in safeguards such as filters in the cornea and
lens that protect against the most harmful rays, like ultraviolet
light, and a yellow pigment that provides extra protection for the
most central point of vision. Retinal pigmented epithelial cells,
which nourish sight-enabling cells in the retina, help gobble up and
dump any resulting tissue trash into the circulation for elimination.
Leftovers show up as fatty, yellow deposits called drusen.

Everyone experiences some age-related vision changes and accumulation
of harmless levels of drusen, Nussbaum said.

But when byproducts start accumulating under the retinal pigment
epithelium, the risk increases for the wet form of macular
degeneration in which fragile new blood vessels grow underneath the
retina, leak and cloud vision. The question is why some people's
condition worsens.

"We see it in one patient and it may stay that way for 20 years. We
see it in another patient and within five years their vision has
functionally started to decrease," said Dr. Emory Patterson, an MCG
School of Medicine graduate completing his ophthalmology residency at
MCG who is helping with the clinical study.

Ganapathy first determined that the eye had the means to tightly
regulate iron levels. Most organs don't have their own system rather
the small intestine regulates absorption of the iron consumed in foods
like beans and tofu.

But Ganapathy found the same genetic mutation that causes
hemochromatosis in a back layer of the retina, which comes in contact
with the blood. A mutation in this HFE gene impairs a protein that
regulates iron absorption. The finding in the mouse eye and human
retinal pigmented epithelial cells was published in 2004 in
Investigative Ophthalmology and Visual Science.

His lab now has animal models for hemochromatosis as well as juvenile
hemochromatosis, which is caused by a different genetic defect and
produces much earlier symptoms.

In the retina of the models, he's finding increased expression of
vascular endothelial growth factors, or VEGF, that enable new blood
vessel growth. This growth is the hallmark of the wet form of macular
degeneration. In fact, anti-VEGF therapies are the most potent
treatments available.

"I tell patients that caught early, they have a 92 percent chance of
stabilizing their vision with anti-VEGF therapy but they only have
about a 38 percent chance of improving their vision," Nussbaum said.
"But at least we can treat it. I also remind them there is not a cure.
It's similar to cancer therapy: we can put them into remission but we
don't know if it will come back."

Most people absorb about 10 percent of the iron they consume. Symptoms
such as joint pain, fatigue, lack of energy, abdominal pain, loss of
sex drive and heart problems indicate excess absorption although many
with the condition have no symptoms when diagnosed.

Source: Medical College of Georgia


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