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work on preventing Blindness from
Age-Related Macular Degeneration and
Newswise, May 26, 2011 —Slowing down the aggregation or “clumping”
of vitamin A in the eye may help prevent
vision loss caused by macular degeneration,
research from Columbia University Medical
Center has found.
Rather than changing the way the eye processes vitamin A, a team of
researchers led by Ilyas Washington, a
professor in the department of ophthalmology
at Columbia’s Harkness Eye Institute,
decided to focus on changing the structure
of vitamin A itself. In turn, Dr. Washington
and his lab have taken a novel step toward
treating age-related macular degeneration
(AMD), a top cause of untreatable blindness
– and Stargardt’s disease, the most common
cause of juvenile macular degeneration.
During the sequence of events that enables vision, vitamin A
undergoes a series of chemical
transformations in the eye. These processes
sometimes allow vitamin A to react with
another molecule of vitamin A to form clumpy
deposits, or what are known as “vitamin A
dimers.” Macular degeneration has long been
thought to be associated with the formation
of these dimers in the eye.
The concentrations of these dimers are higher in the eyes of the
elderly and in those with certain inherited
eye diseases. Vitamin A dimers are also
found together with insoluble pigment
granules called lipofuscin.
In eye diseases such as dry-AMD, the accumulation of vitamin A
dimers and these granules is thought to
happen over decades. But in genetic diseases
such as Stargardt’s disease, this process
can happen much faster, leading to early
vision loss as early as age 8.
“Researchers have tried a different approach to preventing the
formation of vitamin A dimers by modifying
the processing of vitamin A by the eye,” Dr.
Washington says. “But these modifications
seem to have inhibited vision and caused
In animal model studies, Dr. Washington’s lab has set about
synthesizing a modified vitamin A drug
incorporating the hydrogen isotope deuterium
rather than protonium (the more abundant
isotope of hydrogen) at select positions.
Dr. Washington and his lab hypothesized that these modifications
would make the bond involved in dimerization
harder to break, which would slow
dimerization. By feeding this new vitamin A
drug to healthy mice, they were able to
reduce the amount of vitamin A dimers
without any observed side effects, said Dr.
Washington, the Michael Jaharis Assistant
Professor of Ophthalmic Sciences at
When given to mice with the same genetic defect as humans with
Stargardt’s disease, which usually
experience early vision loss, the modified
vitamin A resulted in fewer vitamin A dimers,
better overall ocular health and improved
vision. Importantly, they also observed that
the modified vitamin A behaved exactly as
normal vitamin A does in all other aspects,
making it an attractive potential therapy
for preventing blindness in humans.
This work is detailed in a series of articles published recently in
the Journal of Biological Chemistry,
entitled “Deuterium Enrichment of Vitamin A
at the C20 Position Slows the Formation of
Detrimental Vitamin A Dimers in Wild-type
Rodents” and “C20-D3-vitamin A Slows
Lipofuscin Accumulation and
Electrophysiological Retinal Degeneration in
a Mouse Model of Stargardt’s Disease.”
Dry-AMD affects some 10 million Americans and is the leading cause
of blindness in the Western world. Among
them, approximately 3 million Americans are
at high risk of irreversible vision loss,
and 1 million of them are seriously visually
impaired due to a late form of dry-AMD.
There is currently no treatment for dry-AMD.
Although affecting only 1 in 10,000 individuals, Stargardt’s
disease is the most common form of inherited
macular degeneration and is caused by
mutations in a gene responsible for vitamin
A processing. Altered vitamin A processing
in Stargardt’s leads to faster vitamin A
dimer formation and subsequently lipofuscin
accumulation and to the early onset of
visual symptoms, leading to legal blindness
in almost all cases. There is no current
treatment for Stargardt’s disease.
Dr. Washington’s lab has been awarded a $1.25 million grant from
the National Eye Institute to further
investigate the link between vitamin A
dimers and various retinal degenerations.
The grant will help further the scientific understanding of how
vitamin A dimers, lipofuscin and macular
degenerations are related, and could result
in new approaches to treat these diseases.
Alkeus Pharmaceuticals has licensed from
Columbia certain patents relating to Dr.
Washington’s discoveries and intends to
launch clinical trials for Stargardt’s
disease and dry-AMD.
Columbia University Medical Center provides international
leadership in basic, pre-clinical and
clinical research, in medical and health
sciences education, and in patient care. The
medical center trains future leaders and
includes the dedicated work of many
physicians, scientists, public health
professionals, dentists, and nurses at the
College of Physicians and Surgeons, the
Mailman School of Public Health, the College
of Dental Medicine, the School of Nursing,
the biomedical departments of the Graduate
School of Arts and Sciences, and allied
research centers and institutions.
Established in 1767, Columbia’s College of
Physicians and Surgeons was the first
institution in the country to grant the M.D.
degree and is now among the most selective
medical schools in the country. Columbia
University Medical Center is home to the
most comprehensive medical research
enterprise in New York City and State and
one of the largest in the United States.
Columbia University Medical Center is
affiliated with NewYork-Presbyterian
Hospital, the nation’s largest
not-for-profit, non-sectarian hospital
provider. For more information, please visit