1.What
is Age-related macular degeneration?
Age-related
Macular Degeneration is a disorder which affects cells within the light-sensitive
part of the eye known as the retina. This process typically affects a specialized
region of the retina known as the macula that is responsible for our fine,
central vision. When the macular region of the retina is involved by disease,
a person may have difficulty reading, watching standard televison, and
even recognizing friends.
Age-related
Macular Degeneration (AMD) is the term in general use because the incidence
and prevalence of the disorder increases with age. While other forms of
macular degeneration do occur, AMD is the most common form of the disease
and is the leading caused irreversible visual loss in people over the age
of 60 years in the United States and the Western world. More than 10 million
Americans have some visual dysfunction due to macular degeneration, with
approximately 400,000 individuals developing a severe form of AMD each
year.
2.What
are drusen deposits?
Drusen
are small yellowish deposits of material that accumulate within the deep
retinal layers with time.They are visible to the ophthalmologist when he
or she examines your retina.Drusen “waste deposits” typically develop with
the aging process, and they almost always precede the development of more
severe forms of AMD.It is widely recognized that patients with numerous
and prominent drusen are at a significantly higher risk for developing
visual symptoms from AMD.
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3.What
are the “dry”and “wet”forms
of AMD?
The
more advanced forms of AMD occur in a “dry”or
atrophic type and a “ wet ”or
exudative/neovascular type.The atrophic type is responsible for the large
majority (around 90%) of visual loss due to AMD.A slow loss of central
vision usually occurs over many years in the atrophic form of AMD.Most
patients retain some central vision though they may have difficulty reading
with time. The “wet” form
of AMD, while only occurring in 10% of advanced AMD cases, is responsible
for 90% severe visual loss. In this form, the new blood vessels (“neovascular”)
develop between the layers of the retina. These vessels are abnormal, leak
fluid (“exudative”)
or bleed, and may ultimately leave a central scar in the macula. When detected
early enough, some forms of “wet” AMD may be effectively treated with laser
photocoagulation.
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4.Who
is at risk for AMD?
The
exact cause of AMD is unknown and is probably multifactorial. A leading
risk factor for most individuals is simply getting older. Depending upon
how one defines the disorder, as many as 17% of people over age 60 years
and 30% over age 75 years have some form of AMD in the United States. Caucasian
individuals are at a significantly higher risk than persons of African
or Asian descent, though the disorder is increasingly prevalent among these
individuals as well. Light-colored eyes may have an increased risk compared
with more pigmented eyes. Environmental influences such as extensive exposure
to sunlight may play a role in the pathogenesis of the disorder, and smoking
is known to accelerate the progression of AMD.Another risk factor is the
development of drusen, yellowish “waste deposits” that may accumulate in
the retina with age.
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5.What
are the symptoms of AMD?
In
many cases of AMD, a slow, often imperceptible decline in vision occurs
with time. In some patients, other ocular findings such as a cataract may
contribute to these symptoms, emphasizing the importance of regular eye
examinations with an ophthalmologist. An abrupt disturbance in vision should
be reported promptly as this symptom may indicate the development of “wet”
disease. The acute development of the following symptoms should be reported:
--
blurry or fuzzy vision
--
straight lines, such as sentences on a page or sides of buildings, appear
wavy
--
a dark or empty area appears in the center of vision
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6.Is
AMD a genetic disease?
AMD
is not a classically inherited condition such as cystic fibrosis or hemophilia,
but premature forms of macular degeneration have been well characterized
in some families. No one gene is responsible the pathogenesis of AMD, but
there appears to be a genetic predisposition to its development in some
individuals and families.Because of its manifestation later in life, determining
the precise role of genes in AMD is a difficult biologic challenge.There
are probably many genes that contribute to the development of AMD, but
the precise genes and their interaction with environmental factors remain
largely a mystery.
A
gene on chromosome 1 that is responsible for a juvenile form of macular
degeneration known as Stargardt’s disease or fundus flavimaculatus is the
ABCR gene. Dr. Rando Allikmets, Columbia’s Louis V. Gerstner, Jr. Scholar,
first characterized the ABCR gene in Stargardt’s disease and, in 1997,
identified it as the first gene that may contribute to the pathogenesis
of AMD as many as 16% of all cases. A goal of this study is to further
understand such genes and their influences. If we understand the genes
and their encoded protein products, more targeted therapies to prevent
or treat AMD may be possible.
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7.What
are genes? What is the ABCR gene?
Genes
are the biological units of heredity. They determine obvious traits, such
as skin and eye color, as well as more subtle characteristics, such as
the oxygen-carrying ability of the blood. It is estimated that humans have
30,000 genes. A flaw in virtually any one of them can result in disease.
Each gene acts as a blueprint for making a specific enzyme or other protein.
However, only certain genes in a cell are active at any given moment and,
as cells mature, many of their genes become permanently inactive. It is
the pattern of active and inactive genes in a cell and its resulting protein
composition that determines what kind of cell it is and what it
can and cannot do.
It
is known that genetic factors also contribute to the devolopment of macular
degeneration. The ABCR gene( a retina-specific ATP-binding cassette transporter)
was cloned and characterized in 1997 by Dr. Allikmets and colleagues. The
ABCR protein encoded by the gene acts as a transporter of vitamine A derivates
in both rod and cone photoreceptors.
Mutations
(genetic defects) in this gene were first characterized as causal Stargardt
disease, a common junenile form of macular dystrophy with an estimated
incidence of 1:10,000. Later, Dr. Allikmets and colleagues found an association
between mutations in ABCR and age-related macular degeneration. Currentely,
ABCR is thought to play some role in about 10% of age-related macular degeneration.
ABCR is still the only gene to date that has been implicated in the AMD
complex trait.
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8.What
is DNA?
How is it related to genes?
In
chemical terms, genes are composed of segments of deoxyribonucleic acid,
or DNA. DNA is a very long molecule, composed of individual units called
nucleotides. Each nucleotide contains phosphate, the sugar deoxyribose,
and one of four nucleic acid bases: adenine, thymine, guanine, or cytosine.
It is these bases that carry the information content, or "code," of the
DNA molecule.
To
carry all the information a cellneeds, there must be alot of DNA. In fact,
if you stretched out all the DNA in a singlehuman cell it would be over
one meter long!
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9.What
is gene therapy and what are its objective?
Recent
advances in understanding and manipulating genes -- the biological units
of heredity -- have set the stage for scientists to alter patients' genetic
material to fight or prevent disease. One major goal of gene therapy is
to supply cells with healthy copies of missing or flawed genes. This approach
is revolutionary: Instead of giving a patient a drug to treat or control
the symptoms of a genetic disorder, physicians attempt to correct the basic
problem by altering the genetic makeup of some of the patient's cells.
Hundreds
of major health problems are influenced by gene functions. In the future,
gene therapy could be used to treat many of these conditions. Theoretically,
it could also be used to alter germ cells (egg or sperm) in order to prevent
a genetic defect from being transmitted to future generations. However,
the possibility of germ-line gene therapy is beset by difficult ethical
and social questions (see question 23) as well as technical obstacles.
Gene
therapy could also be used as a drug delivery system. To accomplish this,
a gene that produces a useful product would be inserted into the DNA of
the patient's cells. For example, during blood vessel surgery, a gene that
makes an anticlotting factor could be inserted into the DNA of cells lining
blood vessels to help prevent dangerous blood clots from forming. Many
other conditions might also lend themselves to treatment using this general
approach.
As
medicine operates increasingly on the molecular level, using gene therapy
for drug delivery could save much effort and expense. It could shortcut
the lengthy and complicated process of collecting large amounts of a gene's
protein product, purifying the product, formulating it as a drug, andadministering
it to the patient.
However,
gene therapy is still extremely new and highly experimental. The number
of approved trials is small, and relatively few patients have been treated
to date.
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10.How
is AMD currently treated?
There
are no proven interventions that prevent AMD.If you have been diagnosed
with AMD or are at risk of developing the disorder, it is reasonable to
attempt to decrease the possible risk factors associated with progression
of the disorder. Smoking should be discontinued, and the use of maximal
ultraviolet sunglass protection on bright days should be considered. A
balanced diet including green, leafy vegetables is encouraged.If the naturally
bioavailable sources of vitamins are not a part of your diet, a vitamin
supplement (containing A, E, C, and zinc) may be used.
There
are no medical therapies available to treat the atrophic form of AMD, though
strong spectacles and magnifier may aid reading needs. In some cases the
exudative form of AMD may be treated with laser photocoagulation.For this
reason, all patients with AMD should monitor their vision with an Amsler
grid (graph paper) and report new changes promptly.Imaging studies including
fluorescein and indocyanine green angiography may be used to identify the
source of new blood vessels in exudative disease.Investigational therapies
for exudative AMD include transpupillary thermotherapy, pharmacologic
intervention, and surgery.
Future
directions of treatment of AMD rely upon a better understanding of the
disorder. Identification of genetic factors that play a role in the development
of AMD is a major effort in this regard. Once the responsible genes and
their products are identified, specific therapies will aim to replace faulty
genes, replace their protein products, or provide agents that will improve
the function of the gene product.
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