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Risk Factors for Age-Related Macular Degeneration
On this page, you will find the following:
Risk Factors for Age-Related Macular Degeneration
- Age - The number one risk factor is age. One third of adults over the age of 75 are affected by age-related macular degeneration.
- Smoking - Smoking increases an individual’s chances of developing age-related macular degeneration by two to five-fold. The retina has a high rate of oxygen consumption. Anything that affects the rate of oxygen delivery to the retina has the potential to negatively impact vision. Smoking causes oxidative damage, which is thought to contribute to the development and progression of this disease.
- Family history of macular degeneration - An individual is more likely to be affected by age-related macular degeneration if someone in his or her immediate family has been affected.
- Gender - Females are more likely to be affected by age-related macular degeneration than males. This may be due to the fact that females live longer than males, and thus have more time to develop the disease.
- Race - Caucasians are more likely to be affected age-related macular degeneration than other races. This may be due to differences in genetic background or pigmentation.
- Prolonged sun exposure – Ultra-violet (UV) light damages retinal tissue directly, and can also lead to the accumulation of products that are harmful to the retina.
- A high fat diet, and/or one that is low in nutrients and antioxidants - Individuals with diets high in fat, cholesterol and sugar, and low in antioxidants are more likely to be affected by age-related macular degeneration.
- Obesity - Overweight individuals are more likely to be affected by age-related macular degeneration. An individual with a body mass index (BMI is a measure of body fat) of greater than 30 is 2.5 times more likely to be affected by age-related macular degeneration.
- High blood pressure - Individuals with high blood pressure are more likely to be affected by age-related macular degeneration. High blood pressure, like smoking, leads to a constriction, or narrowing, of the blood vessels that nourish the retina, negatively affecting its health.
- Eye color - Individuals with light-colored eyes are more likely to be affected by dry age-related macular degeneration. This may be due to the fact that light-pigmented eyes offer less protection from damaging UV light.
- Inactivity - Individuals who do not follow a regular exercise routine are more likely to be affected by age-related macular degeneration. In dry age-related macular degeneration, the retina does not receive adequate oxygen, leading to the death of cells in the macula. It is known that exercise improves cardiovascular health, and might prevent an individual from developing this disease.
- The presence of macular degeneration in one eye - If an individual has macular degeneration in one eye, he or she is more likely to develop it in the other eye.
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Heredity & Age-Related Macular Degeneration
Age-related macular degeneration typically affects individuals over 50 years old. Scientific evidence shows that genes may play a role in the development of nearly three out of four cases of this devastating eye disease.
Several genes are believed to be strongly associated with the risk of developing macular degeneration:
- SERPING1 – This gene encodes a protein that inhibits the inflammatory process. SERPING1 prevents the accumulation of inflammatory proteins. There are at least 5 mutations in SERPING1 that inhibit its activity, meaning that toxic inflammatory proteins build up in the blood. These proteins have the ability to negatively affect the retina. Therefore, mutations in SERPING1 have been associated with increased risk of developing AMD.
- Factor H and Factor B genes – these genes are responsible for proteins that help regulate inflammation in the part of the immune system that attacks diseased and damaged cells. According to study results published in 2006 by Columbia University, 74 percent of age-related macular degeneration patients carry certain variants in one or both of these genes, and these may significantly increase their risk of developing it.
- PLEKHA1 – a gene located on chromosome 10; researchers believe it may increase the risk of developing age-related macular degeneration. Like Factors H and B, PLEKHA1 appears to be involved in the cellular processes related to the immune response.
- LOC387715 – A certain variation of this gene appears to increase the risk of developing age-related macular degeneration. This risk is further heightened if a person with this gene variation also smokes. It is highly predictive of developing dry AMD.
- HTRA1 –. Mutations in the HTRA1 gene, which flanks the LOC387715 gene, have been shown to both increase and decrease the risk of developing AMD
- Complement C3 – This gene is another member of the complement cascade (the body’s immune response) that has been found to be associated with the development of AMD.Additionally, C3 has been found in drusen. Having a particular variant of the C3 geneincreases an individual’s chances of developing AMD by 70-200%.
- CFH – Complement Factor H (CFH) is a gene with a known role in the development of age-related macular degeneration. CFH is involved in mediating the immune response. Specifically, CFH inhibits the immune response and associated inflammation. When CFH is mutated, it activates these processes. 30-50% of patients with age-related macular degeneration have a mutation in CFH. This finding suggests that the inflammatory process is involved in the development of age-related macular degeneration.
- CRP – Levels of the inflammatory marker C-Reactive Protein (CRP) are increased in the blood of patients with macular degeneration. High levels of CRP are damaging to cells and tissues of the body. High levels of CRP are associated with both intermediate and advanced macular degeneration. In fact, high levels of CRP lead to a 65% increased risk of developing macular degeneration. This finding provides additional evidence of inflammation’s role in macular degeneration’s development.
- CFB/C2 – Complement Factor B (CFB) and Complement Component 2 (C2) are two genes that activate the complement cascade and the immune response, which is involved in the development of macular degeneration. Mutations in both of these genes can predict the development and severity of macular degeneration.
- HMCN1/FBLN6 – In 2003, Hemicentin-1 (HMCN1)/Fibulin-6 (FBLN6) was identified as the first gene tied to the development of macular degeneration. Mutations in the HMCN1 gene were found in many members of a multi-generational family that had macular degeneration. These genes may be involved in drusen formation, one of the earliest hallmarks of dry macular degeneration.
- FBLN5 – In 2004, Fibulin-5 (FBLN5) was identified as the second gene related to macular degeneration. FBLN5 is involved in maintaining the integrity of the retina in the specific region where drusen form. Any change in retinal integrity could lead to a higher likelihood of macular degeneration development. In fact, scientists believe that a mutation in FBLN5 may lead to the formation of drusen, which indicate early dry age-related macular degeneration.
- TLR3 – In 2008, scientists identified the first gene involved in the advanced form of dry macular degeneration, called geographic atrophy. Toll-Like Receptor 3 (TLR3) is involved in the body’s immune response. If something activates TLR3, it attacks infected cells, and in the case of dry macular degeneration, it attacks the light-sensitive cells in the retina. Mutations in TLR3 that render it less active or inactive in essence prevent the death of retinal cells, thereby providing protection against geographic atrophy.
- ApoE – Apolipoprotein E (ApoE) packages cholesterol and other fats and transports them through the bloodstream. ApoE is also involved in the neurodegeneration that occurs in Alzheimer’s disease. There are several variations, or alleles, of the ApoE gene. One of the alleles appears to protect individuals from macular degeneration, and one of the alleles appears to increase an individual’s risk of developing macular degeneration. It appears that ApoE is a susceptibility gene for age-related macular degeneration.
- CD36 – Cluster of Differentiation 36 (CD36) is a “scavenger receptor,” and scavenges many toxic substances so that they do not lead to cell death. In 2008, scientists discovered that a deficiency in CD36 leads to the death of light-sensitive cells in the retinas of mice and rats. The scientists suggest that CD36 therapy is a way to prevent cell death and blindness in dry macular degeneration.
- IL-6 and IL-8 – The interleukins (ILs) are blood-borne factors that mediate the body’s immune responses. ILs indicate inflammation, one of the factors involved in dry macular degeneration development and progression. One of the ILs, IL-6, has recently been found to be increased in patients with macular degeneration. IL-6, therefore, may be used as a biomarker to identify patients with increased risk of developing macular degeneration. Mutations in another IL, IL-8, promote inflammation and have been shown to increase a patient’s risk of macular degeneration. These findings are further proof of the role of inflammation in the development and progression of macular degeneration.
- CCL2 – Chemokine (C-C motif) Ligand 2 (CCL2) is a secreted protein that is involved in the immune response. CCL2 has also been shown to prevent cell death. If CCL2 can prevent the death of light-sensitive cells in the retina, patients with macular degeneration might not lose their vision. Researchers have shown that mice that are missing the CCL2 gene develop features of macular degeneration. CCL2, then, may represent a potential therapeutic target for the treatment of macular degeneration.
Other gene candidates are being studied to determine their role in macular degeneration. While there is definitely a strong genetic component to this disease, it is highly likely that its development is due to a combination of multiple factors including gene mutations or variations and environmental factors such as sunlight exposure, diet and smoking.
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Protecting Eye Health and Possible Prevention against Macular Degeneration
Healthy Lifestyle, Healthy Eyes
The following suggestions will help protect your vision, improve your overall health, and potentially lower your risk of developing macular degeneration:
- Eat a varied and nutritious diet that includes leafy green vegetables, fruit, fish and foods containing vitamins D, E and C, beta carotene and omega-3 fatty acids. Read below for more information on healthy “vision” foods.
- Exercise regularly. Individuals who break a sweat at least three times per week demonstrate a 25% reduction in the rate of progression to advanced age-related macular degeneration.
- Maintain a healthy weight.
- Keep blood pressure at a normal level (normal blood pressure is defined as 120/80. A blood pressure higher than 120/80 places you at an increased risk for developing dry age-related macular degeneration.
- Do not smoke. The risk of developing age-related macular degeneration is 2-3 times higher in smokers (and ex-smokers) than non-smokers. Importantly, research has shown that individuals can reduce their chances of developing dry age-related macular degeneration by quitting smoking. Although beta carotene supplements have been shown to slow the progression of age-related macular degeneration, if you are a current or ex-smoker, you should not take these supplements because they may lead to an increased risk of lung cancer.
- Prevent overexposure to sunlight by wearing sunglasses and hats.
- Regularly visit an eye doctor for comprehensive eye exams.
- Perform Amsler grid tests at home.
“Vision” Foods to Include in Your Diet
- Dark green, yellow and orange fruits and vegetables. These contain carotenoids which may defend against a number of medical conditions, including age-related macular degeneration. Lutein and zeaxanthin are two especially important carotenoids related to vision health. Lutein is found in dark, leafy greens such as spinach, collard greens and kale, as well as in okra, broccoli, papaya, oranges, kiwi, mango, green beans, peaches, sweet potatoes, lima beans, squash, red grapes and green bell pepper. Egg yolks also contain lutein. Yellow corn, honeydew melon, squash, oranges, mango, kale, apricots, peaches and orange bell pepper are good sources of zeaxanthin.
- Fruits and vegetables abundant in vitamin C including green peppers, citrus fruits, tomatoes, broccoli, strawberries, yams, leafy greens and cantaloupe.
- Eggs, fortified cereals, fruit, wheat germ, green leafy vegetables, nuts, nut oils, vegetable oils and whole grains. These all contain vitamin E.
- Wild salmon, tuna, sardines, walnuts and flaxseed oil. These are good sources of omega-3 fatty acids.
- Whole grain versions of rice, bread and pasta that contain complex carbohydrates which are metabolized more slowly and are healthier than their “white” counterparts. (White rice, bread and pasta have a high glycemic index meaning that the carbohydrates are broken down rapidly into glucose or blood sugar. They provide quick energy but contain few nutrients and little fiber, and in large amounts they may damage cells. Some studies have shown that eating foods with a high glycemic index may increase the risk of developing macular degeneration.
Special Vitamins for Dry Macular Degeneration
The National Eye Institute’s Age-Related Eye Disease Study (AREDS) found that taking a specific high dose formula of antioxidants and zinc (500 milligrams of vitamin C, 400 International Units of vitamin E, 15 milligrams of beta-carotene, 80 milligrams of zinc as zinc oxide, and two milligrams of copper as cupric oxide) may delay or prevent intermediate age-related macular degeneration from progressing to the advanced stage. The antioxidant vitamins and minerals in the AREDS formula help maintain healthy cells and tissues and may prevent damage in the macula. There is no evidence, however, that the AREDS formula provided any benefit to people with early stage age-related macular degeneration. Patients with intermediate age-related macular degeneration in one or both eyes or advanced age-related macular degeneration (dry or wet) in one eye but not the other eye should consider taking the formula. Always consult a physician before taking any supplements. The AREDS formula may be contraindicated due to other medical conditions or other medications.
The NEI has begun AREDS-2 trials focused on the addition of lutein, zeaxanthin and omega-3 fatty acids to the original AREDS formula. Researchers are interested in the effect of these supplements on the progression to advanced age-related macular degeneration and/or moderate vision loss in those at risk of progression. Participants will also be offered variations on levels of beta-carotene and zinc that were included in the original AREDS formula. Scientists will follow up for at least five years.
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Further Information
The following publications from AHAF can provide you with more information:
- Living with Macular Degeneration
- Macular Degeneration. The Essential Facts
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Source: Some of the information in this section of our website was obtained from the National Eye Institute and the National Library of Medicine. The American Health Assistance Foundation is grateful to Jeffrey H. Stern, M.D., Ph.D. at the Regenerative Research Foundation and Susan E. Yanni at Vanderbilt University for reviewing aspects and providing some of the above content.
Last Reviewed On: 12/18/09
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