Age-Related
Macular Degeneration
(AMD)
Aptamer Applications:
Age-Related Macular Degeneration (AMD) is an eye disorder that is the leading cause of vision loss in people fifty years of age and older. 1.8 million people are afflicted by this disease, with another 7.3 million at substantial risk of being affected.
What is AMD?
AMD is caused by the deterioration of the Macula. The Mac-
ula is a small but extremely vital section of the Retina. The Retina is the
light-sensing layer in the back of the eye. The Macula is what allows us
to perform highly detailed tasks - such as threading a needle and rea-
ding small print - and is also essential to central vision.
AMD develops as a byproduct of the body's natural aging process.
There are two types of AMD.
1. Dry or Atrophic Age-Related Macular Degeneration - The more common form, the "dry" form of AMD is caused by the buildup of drusen - yellow or white deposits that accumulate over a person's lifetime. As drusen grow in number and size, vision is distorted or dimmed. As this form of AMD progresses, the light-sensitive tissue layer of the eye begins to thin, and then eventually atrophies (die). Blind spots begin to appear in the center of the patient's vision, and if untreated, leads to complete loss of central vision.
2. Wet Age-Related Macular Degeneration - Although affecting a smaller group of people then the "dry" form, the "wet" form of AMD is much more serious. Wet AMD is an advanced form of Dry AMD, and is caused by abnormal growth of blood vessels in a layer underneath the retina called the choroid. This abnormal vessel growth is caused by a hormones released by inflammatory cells called Vascular Endothelial Growth Factor (VEGF). Normally, VEGF is released to increase oxygen flow to the eye. However, in these circumstances, the blood vessels leak and disrupt vision. This occurs faster then Dry AMD and results in blind spots, loss of central vision, and making straight lines appear "wavy." The blood vessels eventually scar, making vision loss permanent.
cells, without a continuing flow of VEGF, die off - thus treating Wet AMD. Macugen is administered in 0.3 mg doses every 6 weeks by intravitreal injection - injection directly into the eye. The aptamers travel through the eye, locate, and then bind to VEGF with the high specificity and affinity of aptamers.
Pegaptanib is a 27 nucleotide long aptamer, with purine chemical modification and inverted nucleotide caps to resist nuclease degradation. It is also conjugated to PEG to increase size, which slows tissue absorption and renal filtration - lengthening half-life.
Although the drug sold well initially with high success rates, the introduction of the Monoclonal Antibody-based Lucentis, which is able to bind to all forms of VEGF including VEGF121 stole much of the market away from Macugen.
Diagram of the eye with the Retina and Macula labeled.
Diagram of the eye with the Retina and Macula labeled.
Images of both the "wet" and "dry" form of AMD. The "wet" AMD shows the fluid disrupting vision, and the "dry" AMD shows drusen.
Images of both the "wet" and "dry" form of AMD. The "wet" AMD shows the fluid disrupting vision, and the "dry" AMD shows drusen.
What central vision loss looks likes
What central vision loss looks likes
Video Citation 12: Video goes into more depth then the explanation above - however, there is good visual representation of the process behind Wet AMD.
AMD Symptoms and Risk Factors
The following increase risk for AMD:
1. Smoking
2. High Blood Pressure (Hypertension)
3. Obesity
4. High Cholesterol
5. Race - Caucasians are more prone to be afflicted by AMD
6. Hereditary Predisposition - Genetics, as inherited, can increase risk for AMD.
Symptoms include:
1. Blurring of words when reading
2. Gaps in vision - missing pieces of images
3. Need for increased light for close vision
4. Faded colors
5. Habit of looking slightly to the side to see clearly
6. Distorted or wavy lines
Macugen -
An Aptamer-Based Solution
Pegaptanib Sodium, with the brand name Macugen, is an aptamer-based treatment for Wet AMD. Approved in December 2004 by the Food and Drug Administration, and marketed by Pfizer and Eyetech, Macugen was the first drug targeting VEGF and the first aptamer-based drug.
How Does Macugen Work?
Pegaptanib is an aptamer-based drug targeting VEGF, binding to all forms of the growth factor except the smallest, which is called VEGF121. It inhibits interactions between VEGF and its receptors, preventing VEGF from stimulating blood vessel growth. Existing blood
Macugen dose with injector
Macugen dose with injector
Image showing intravitreal injection
Image showing intravitreal injection
Diagram of the eye
Diagram of the eye