Macular DegenerationLife Extension Suggestions
Pathology of AMD
The retina is the innermost layer of the eye, which contains nerves that communicate sight. Behind the retina is the choroid, which supplies the blood to the macula and retina. In the atrophic (dry) form of AMD, cellular debris called drusen accumulate between the retina and the choroid. The macular degeneration progresses slowly with vision lost painlessly. In the wet form of AMD, blood vessels below the retina undergo abnormal growth into the retina beneath the macula. These newly formed blood vessels frequently bleed, causing the macula to bulge or form a mound, often surrounded by small hemorrhages and tissue scarring. The results are a distortion in central vision and the appearance of dark spots. Whereas the progression of atrophic AMD may take place over years, neovascular AMD can progress in mere months or even weeks (de Jong 2006).
While the exact causes of AMD are not fully understood, recent scientific evidence points to chronic vascular disease, including cardiovascular disease, as a potential cause. Scientists believe that slow degradation of the blood vessels in the choroid, which provides blood to the retina, may lead to macular degeneration.
A complementary theory suggests an alteration in the dynamics of the choroidal blood circulation as an important pathophysiological mechanism. Blockages within the choroidal blood vessels, possibly due to vascular disease, lead to increased ocular rigidity and decreased efficiency in the choroidal blood circulation system. Specifically, the increased capillary resistance (due to blockages) causes elevated pressure, resulting in the extracellular release of proteins and lipids that form deposits known as drusen (Kaufmen 2003).
Cholesterol exists within the drusen. Researchers suggest that the formation of AMD lesions and their aftermath may be a pathological response to the retention of a sub-endothelial apolipoprotein B, similar to a widely accepted model of atherosclerotic coronary artery disease (Curcio 2010). As such, researchers have now found that bio-markers predictive of cardiovascular risk (e.g., elevated homocysteine and C-reactive protein (CRP) levels) are risk factors for AMD (Seddon 2006).
Small drusen are extremely common, with approximately 80% of the general population over 30 manifesting at least one. The depositing of large drusen (≥ 63µm) are characteristic of atrophic AMD, in which this drusen causes thinning of macular tissue, experienced as blurry or distorted vision with possible blank spots in central vision. Drusen continue to accumulate and aggregate with advancing age; those over 75 are 16 times more likely to develop aggregated large drusen compared to those 43-54 (Klein 2007).
Along with drusen formation, there may be deterioration in the elastin and collagen in Bruch’s membrane—the barrier between the retina and the choroids—causing calcification and fragmentation. This, coupled with an increase in a protein called vascular endothelial growth factor (VEGF), allows capillaries (or very small blood vessels) to grow up from the choroid into the retina, ultimately leading to blood and protein leakage below the macula (wet form AMD) (Friedman 2004; Bird 2010).
Other theories postulate that abnormalities in the enzymatic activity of aged retinal pigment epithelium (RPE) cells lead to the accumulation of metabolic byproducts. When the RPE cells become engorged, their normal cellular metabolism is obstructed, resulting in extracellular excretions that produce drusen and lead to neovascularization.
People who have a close relative with AMD have a 50% higher risk of eventually developing it compared to 12% for other people. Scientists believe a newly discovered genetic association will better help predict those at risk and ultimately lead to better treatments (Patel 2008).