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Increasing intake of the omega-3 fatty acids DHA and EPA, found in popular
fish-oil supplements, may protect against blindness resulting from
abnormal
blood vessel growth in the eye, according to a study published online by
the
journal Nature Medicine on June 24. The study was done in mice, but a
clinical trial at Children's Hospital Boston will soon begin testing the
effects of omega-3 supplementation in premature babies, who are at risk
for
vision loss.
Abnormal vessel growth is the cause of retinopathy of prematurity,
diabetic
retinopathy in adults, and "wet" age-related macular degeneration, three
leading causes of blindness. Retinopathy, affecting about 4 million
diabetic
patients and about 40,000 premature infants in the United States, is a
two-step disease that begins with a loss of blood vessels in the retina
(the
nerve tissue at the back of the eye that sends visual signals to the
brain).
Because of the vessel loss, the retina becomes oxygen-starved and sends
out
alarm signals that spur new vessel growth. But the new vessels grow
abnormally and are malformed, leaky and over-abundant. In the end stage of
the disease, the abnormal vessels pull the retina away from its sup****ting
layer, and this retinal detachment ultimately causes blindness.
The researchers, led by Lois Smith, MD, PhD, and Kip Connor, PhD, of
Children's Hospital Boston's Department of Ophthalmology and Harvard
Medical
School, and John Paul SanGiovanni, ScD, of the National Eye Institute
(NEI),
National Institutes of Health, studied retinopathy in a mouse model,
feeding
the mice diets that emphasized either omega-3 fatty acids (comparable to a
Japanese diet) or omega-6 fatty acids (comparable to a Western diet).
Mice on the omega-3 diet, rich in DHA (docosahexaenoic acid) and its
precursor EPA (eicosapentaenoic acid), had less initial vessel loss in the
retina than the omega-6-fed mice: the area with vessel loss was 40 to 50
percent smaller. As a result, the omega-3 group had a 40 to 50 percent
decrease in pathological vessel growth.
"Our studies suggest that after initial loss, vessels re-grew more quickly
and efficiently in the omega-3-fed mice," says Connor, the study's first
author. "This increased the oxygen supply to retinal tissue, resulting in
a
dampening of the inflammatory 'alarm' signals that lead to pathologic
vessel
growth."
Because omega-3 fatty acids are highly concentrated in the retina, a mere
2
percent change in dietary omega-3 intake was sufficient to decrease
disease
severity by 50 percent, the researchers note. Validating their findings,
results were virtually identical in mice whose omega-3 fatty acid levels
were increased through genetic means.
Omega-3 fatty acids like DHA and EPA are thought to dampen inflammation in
the body. They are often lacking in Western diets; instead, omega-6 fatty
acids predominate. The ideal omega-6:omega-3 ratio is thought to be 2:1 to
5:1, whereas typical Western diets have ratios of 10:1 or higher.
Premature
infants are especially lacking in omega-3 fatty acids, because they miss
getting this nutrient from their mothers, a transfer that normally happens
in the third trimester of pregnancy.
The researchers demonstrated that the omega-3-based diet suppressed
production of TNF-alpha, reducing the inflammatory response in the retina,
whereas the omega-6-based diet increased TNF-alpha production. The retinas
of omega-3-fed mice also had increased production of the anti-inflammatory
compounds neuroprotectinD1, resolvinD1 and resolvinE1. These compounds,
derived from omega-3 fatty acids, also potently protected against
pathological vessel growth, and they were not detected in the retinas of
mice fed the omega-6 diet.
"If omega-3 fatty acids, or these anti-inflammatory mediators, are as
effective in humans and they are in mice, simple supplementation could be
a
cost-effective intervention benefiting millions of people," says Smith,
the
study's senior investigator. "The cost of blindness is enormous."
Aside from fish-oil supplements, the most widely available source of
omega-3
fatty acids is coldwater oily fish (wild salmon, herry, mackerel,
anchovies,
sardines). The compounds can also be made synthetically from algae or
other
non-fish sources.
Paul A. Sieving, MD, PhD, director of the NEI, which provided funding for
the study, said, "This study shows the benefit of dietary omega-3 fatty
acids in protecting against the development and progression of retinal
disease. It gives us a better understanding of the biological processes
that
lead to retinopathy and how to intervene to prevent or slow disease. It
will
be interesting to see if human clinical trials show similar beneficial
effects."
The clinical trial at Children's Hospital Boston will follow premature
newborns who are unable to feed and are receiving parenteral nutrition,
with
omega-3 fatty acids as part of their IV solution. The hope is that the
omega-3 supplementation will allow the retina and its vessels to develop
normally. "Once the retina is detached, there's little you can do," says
Smith. "We want to give omega-3 right from the beginning to mimic what the
infants would be getting from their mothers in utero, had they not been
born
prematurely."
In addition to retinopathy, the researchers speculate that omega-3 fatty
acids may help reduce vision loss in people with "wet" or neovascular
phase
of age-related macular degeneration (AMD), a disease that also involves
abnormal vessel growth. This possibility is now being explored in a large,
NEI-funded clinical trial called AREDS2, coordinated by Emily Chew and
John
Paul SanGiovanni, both co-authors of the animal study. (See
www.nei.nih.gov/neitrials/viewStudyWeb.aspx?id=120.)
Drugs that block the growth factor VEGF are also being studied in the end
stages of retinopathy of prematurity and diabetic retinopathy, and have
been
approved for use in "wet" AMD, Smith notes. While injection of anti-VEGF
compounds into the eye can block pathological vessel growth in the retina,
omega-3 supplementation may reduce the need for repeated injections by
preventing some patients from advancing to end-stage disease, she says.
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