Might Means of Reversing Atherosclerosis also Prevent Macular Degeneration?

Atherosclerosis is characterized by growing lipid deposits that weaken and narrow blood vessels. Age-related macular degeneration is also characterized by a deposition of lipids in and around the retina in its early stage. One might therefore speculate as to whether age-related problems with the mechanisms responsible for clearing lipids might be at the root of both conditions. Macrophages are the cell responsible for gathering up unwanted lipids, which they then hand off to HDL particles for the journey back to the liver and consequent excretion, a process known as reverse cholesterol transport. This system works well in enough in youth, but falters with age. Macrophages become dysfunctional, with one theory being that this is due to increasing levels of oxidized lipids that cannot easily be broken down, and thus clog up the vital functions of macrophage cells.

A sizable amount of research into reverse cholesterol transport has taken place in the context of atherosclerosis, and this has given rise to a varied set of attempts to increase the flow of cholesterol through macrophages. So far this has resulted in failed clinical trials and limited benefits to patients, but efforts continue on the next generation of potential therapies. Less work has taken place in the context of macular degeneration. The authors of the open access paper here disable reverse cholesterol efflux in mice and observe the resulting deposition of lipids in the retina, making the argument that the results indicate that the situation is much the same as in atherosclerosis. Thus methods of treating atherosclerosis that are based on improved rates of reverse cholesterol transport may also turn out to prevent macular degeneration.

Advanced age-related macular degeneration (AMD), the leading cause of blindness among people over 50 years of age, is characterized by atrophic neurodegeneration or pathologic angiogenesis. Early AMD is characterized by extracellular cholesterol-rich deposits underneath the retinal pigment epithelium (RPE) called drusen or in the subretinal space called subretinal drusenoid deposits (SDD) that drive disease progression. However, mechanisms of drusen and SDD biogenesis remain poorly understood. Although human AMD is characterized by abnormalities in cholesterol homeostasis and shares phenotypic features with atherosclerosis, it is unclear whether systemic immunity or local tissue metabolism regulates this homeostasis.

Here, we demonstrate that targeted deletion of macrophage cholesterol transporters ABCA1 and ABCG1 leads to age-associated extracellular cholesterol-rich deposits underneath the neurosensory retina similar to SDD seen in early human AMD. These mice also develop impaired dark adaptation, a cardinal feature of RPE cell dysfunction seen in human AMD patients even before central vision is affected. Subretinal deposits in these mice progressively worsen with age, with concomitant accumulation of cholesterol metabolites including several oxysterols and cholesterol esters causing lipotoxicity that manifests as photoreceptor dysfunction and neurodegeneration.

These findings suggest that impaired macrophage cholesterol transport initiates several key elements of early human AMD, demonstrating the importance of systemic immunity and aging in promoting disease manifestation. Polymorphisms in genes involved with cholesterol transport and homeostasis are associated with a significantly higher risk of developing AMD, thus making these studies translationally relevant by identifying potential targets for therapy.

Link: https://doi.org/10.1172/jci.insight.120824


Off Topic Regarding Medical Tourism: Big Medicine Strikes Back


How many of you thought big medicine in the West was going to allow medical tourism to be our escape from their sick care monopoly, in pursuit of FDA-unapproved rejuvenation and healing alternative therapies? Think again. Look for similar actions in Thailand next.

Posted by: Tom Schaefer at September 11th, 2018 12:09 PM

@Tom Schaefer, armed raid is harsh, but to be fair, those "natural cancer clinics" are pure scam, preying on desperate people, sucking every last bit of money out of them, before vast majority of them succumbs. You have countless youtube videos of people rejecting conventional therapies and opting for these quacks, simply based on some bogus anecdotal evidence.. In reality this is a death trap for some people, who could otherwise perhaps be cured. That's why these clinics are growing like mushrooms in Tijuana, Mexico, charging anywhere from 1.000 to 50.000 for different "therapies", depending on how much you can muster.

Posted by: DarwiN at September 11th, 2018 2:05 PM
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