Tuesday, September 9, 2008

The Causes and Prevention of AMD

With an aging population vision deterioration is rapidly becoming a major health concern. Fortunately there are a number of measures we can undertake to markedly reduce the risk of vision loss with age. There are two principle visual pathologies that occur with aging. “Dry” Age related Macular Degeneration and “wet” AMD. Dry AMD predominates and involves the gradual build up of drusen. Wet AMD is probably also initiated by drusen accumulation but what happens is the sprouting of new blood vessels, probably as an attempt to restore circulation. Unfortunately these blood vessels tend to be “leaky”, spilling their contents into the retina and direct exposure to blood is often toxic to neurons. Wet AMD(also called, “exudative AMD”) only constitutes about 10% of all AMD cases and is very difficult to treat. We will focus on the more common Dry AMD because there are a number measures the individual can take to both prevent is occurrence and moderate its progression once diagnosis has been made.

The Current Understanding of the causes of Dry AMD

In dry AMD former the presence of drusen, a fatty deposit in the the main visual area of the retina(macula), can be seen by an optometrist. While not in itself indicative of AMD, the gradual accumulation of drusen is a warning sign that all is not well with your vision. Whether or not drusen is a serious indicator of emerging pathology depends on the types and density of drusen. Many people over 50 will have some levels of drusen. With increasing longevity it is essential that there is more public awareness of how to protect the retina so that good vision is maintained throughout the greater part of life. Until recently it was presumed that once drusen was present it could not be eliminated. In a follow up post on vision I will provide some background to this new supplement which will provide insights as to its efficacy.

Why is vision loss so common with age?

The retina is amongst the most vulnerable regions of the Central Nervous System. Technically the retina is part of the Central Nervous System. The layer of cells that play a critical role in protecting retinal neurons is called the Retinal Pigment Epithelium(RPE). Some researchers have claimed that the RPE cells are the most active in the body, constantly providing nutrition to the retina whilst simultaneously eliminating waste products from the eye. Presently the evidence indicates that it is the gradual diminution of waste product degradation and elimination that gives rise to drusen accumulation.

The elimination of waste products from the retina is a very complex process involving a number of steps. Dysfunction at any of these steps can give rise to the gradual accumulation of lipofuscin(proteins, fat combinations mostly, but with many other elements present) and subsequent pathology. For example, a number of juvenile macular degeneration pathologies involve a change in one gene that inhibits the waste removal process. The ongoing accumulation of waste products, which may have commenced at birth, gradually gives rise to a visual pathology and can result in total blindness. Recent trials of gene vector therapy hold out considerable hope that these conditions will soon be treatable.

The Nutshell Description of Waste Removal from the Retina

A key and initial component of light signaling in the retina is a part of the receptor cells called Photoreceptor Outer Segments(POS). These long segments are being constantly created and utilised in vision. These segments are periodically shed from the POS and it is vital these are rapidly transported to the RPE where degradation can commence. The problem with these segments is that these are very easily oxidised and can then become attached to proteins, thus the emergence of lipofuscin deposits and subsequent drusen formation in the retina. Once these oxidation processes occur it can be much more difficult, and in some cases perhaps impossible, for the RPE to absorb(phagocytosis), degrade, and pass on the waste products to the circulation. In Dry AMD the accumulation appears to mainly at the waste product elimination level, thus drusen is frequently present between Bruch’s Membrane- a membrane that separates the RPE from the choroid, where blood vessels are present. I suspect this failure to eliminate drusen is also arising because of insufficient degradation in the RPE. Undoubtedly, as we learn more, the picture will become more complex.

Why does this Problem Increase with Age?

As we age there is a general reduction in reparative processes. Healthy living can ameliorate this somewhat but in relation to the retina this loss of function plays a critical role in degenerative processes. Lifestyle and dietary changes are very important in preventing this ongoing loss of function reaching a critical level where secondary, possibly inflammatory immune mediated processes, come into play and accelerate the rate of tissue destruction.

The accumulation of waste products has been demonstrated to impair these reparative processes. As these products accumulate in the retina a vicious cycle ensues: the more waste products present, the less efficiently the waste product removal processes function. These waste products induce oxidative processes, thereby adding another dimension to the problem. This is a lifelong process so the lesson here is: maintaining good vision with age begins in our teenage years.

What are the Risk Factors for AMD?

  • Smoking, particularly in relation to the much more severe wet AMD.
  • Poor oxidation status. That is, insufficient dietary intake of antioxidants, particularly lutein and zeaxanthin, both of which are found in very high levels in the retina.
  • There is evidence to suggest that lifelong exposure to strong sunlight can accelerate the accumulation of lipofuscin. Wear high quality sunglasses with “wrap around” features.
  • Deprivation of oxygen supply to the retina. Regular aerobic exercise is very important for retinal health.
  • Poor sugar regulation, as occurs in Diabetes, is probably a risk factor. Diabetes is a leading cause of blindness.
  • Fatty acid intake. DHA, an omega 3 fat, is a precursor to NPD1, an neuroprotective agent very important for retinal health. Numerous authorities now assert that a chronic deficiency in omega 3’s, especially if there is an excess of omega 6 fats in the diet, can be a causative factor in many age related conditions.
  • Cardiovascular Disease. Loss of blood supply and clogged blood vessels can have serious implications for retinal health.
  • Obesity, possibly because of its association with cardiovascular disease and high triglyceride\cholesterol levels, but also chronic obesity tends to increase systemic inflammation.

Strategies to reduce the risk of AMD

  • Stop smoking.
  • Include generous portions of leafy greens in your diet. While the epidemiological data on antioxidant intake and the risk of AMD is conflicting, at this point in time it is prudent to make sure your diet contains good levels of lutein and zeaxanthin in the diet. Apart from these important antioxidants, a well balanced diet, particularly in relation to fats, is vital for overall health. Strange as it may sound, an egg a day is worth considering because eggs are highly nutritious and rich in lutein and zeaxanthin. Contrary to popular opinion, eggs are not a significant risk factor for cardiovascular disease, some authorities even assert the opposite.
  • Vitamin A\beta carotene levels need to be maintained. However there is some data to suggest that high levels of these may very slightly increase the risk of AMD. If you are a smoker, there is now a general consensus that high beta carotene intake will increase the risk of lung cancer. Unfortunately there is also data suggesting that beta carotene may help prevent emphysema. A further complicating factor here is a recent study the results of which suggested that beta carotene supplements had no effect on AMD prevalence. Supplements of vitamin A and beta-carotene should not be required. If a person is deficient in Vitamin A then there is something seriously wrong with their diet.
  • If you have high cholesterol and\or blood pressure, do something about it. High blood pressure is a risk factor for Wet AMD and a host of other pathologies.
  • Wear sunglasses. A key driver of oxidative processes in the retina is light, especially UV light and there evidence to suggest that blue light might also be a risk factor. Make sure you buy high quality sunglasses that wrap around your eyes and have strong UV inhibiting properties.
  • Eat fish regularly to maintain your omega 3 levels. Not too often though and be careful, there are now many studies indicating that the oceans are so polluted that heavy fish consumption can result in the accumulation of dangerous chemicals and metals in our body. The general recommendation is 3 times a week. I think the time is rapidly approaching when even that level of consumption will become problematic. We must stop poisoning the oceans.
  • Over 40 years of age, have regular eye checkups, including retinal examinations. Ask your doctor about any the presence of drusen\lipofuscin. If your doctor suggests it could be a problem in your case, ask if a retinal image is a good idea so that on latter examinations a comparison can be made.
  • Exercise. Regular aerobic exercise is vital to our overall health.

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