Restoring Autophagy as a Basis to Treat Macular Degeneration

The blindness of age-related macular degeneration is linked to the build up of lipofuscin in cells, a hardy collection of metabolic waste products that the body cannot effectively break down. Lipofuscin accumulates to cause progressive failure of the cellular recycling and maintenance mechanisms known as autophagy - this is due to failing lysosomes, a part of the autophagic machinery which becomes increasingly clogged and bloated by lipofuscin.

Macular degeneration is one of the better known manifestations of this process, but it happens in long-lived cells throughout the body. The SENS proposals for rejuvenation therapies include the use of bacterial enzymes to break down the components of lipofusin, so as to restore autophagy and remove this contribution to degenerative aging. The open access research into autophagy and macular degeneration quoted below supports the SENS view on how best to proceed:

A new [study] changes our understanding of the pathogenesis of age-related macular degeneration (AMD). The researchers found that degenerative changes and loss of vision are caused by impaired function of the lysosomal clean-up mechanism, or autophagy, in the fundus of the eye. The results open new avenues for the treatment of the dry form of AMD, which currently lacks an efficient treatment.

AMD is a storage disease in which harmful protein accumulations develop behind the retina. These accumulations are indicative of the severity of the disease. As the disease progresses, retinal sensory cells in the central vision area are damaged, leading to loss of central vision. The cell biological mechanisms underlying protein accumulations remain largely unknown.

For the first time ever, the present study showed that AMD is associated with impaired lysosomal autophagy, which is an important clean-up mechanism of the fundus of the eye. This renders the cells in the fundus of the eye unable to dispose of old, deformed or otherwise faulty proteins, which, in turn, leads to the development of protein accumulations and loss of vision. The study can be regarded as a breakthrough, as the results change our understanding of the pathogenesis of AMD and also open new avenues for the treatment of the dry form of AMD. Drugs inhibiting the impairment of autophagy could possibly even stop the progression of AMD.

Link: http://dx.doi.org/10.1371/journal.pone.0069563

Comments

What about Beta Amyloid?
Looking through the research it appears that Beta Amyloid (as in Alzheimer's) is the cause of Age-related Macular Degeneration. And conversely, that failing autophagy and mitochondria are the cause of Dementia.

But I'm reassured that every time an alternative cause is suggested for some disease of aging, that SENS therapies are already targeting the other cause for some other reason.

Posted by: Carl at August 23rd, 2013 2:15 AM

It is great that research is ongoing into AMD, but I have total dry AMD and am desperate for a cure. I am 78 years old so I don't expect much sympathy, but I am very fit and healthy. I have been on a Keto eating plan with intermittent fasting to encourage autophagy for six months and intend to stay on it. So^ far there has been no improvement in my eyesight. Is there no hope of an improvement of AMD for me?

Posted by: Mike Bearsley at May 12th, 2019 11:57 PM

I am at the very early onset of AMD with drusen in my eyes. I noticed that Mike Bearsley above commented that he is on keto with no change in his drusen. My drusen dx was only since I have been following keto... coincidence or too much emphasis on fats? I agree with the low-carb aspect regarding insulin response, but I am now beginning to shift to only healthy fats, less animal protein, much more plant-based with intermittent fasting. I used to believe in keto and eschew most medical doctors, but now I respect their knowledge. In the end, I don't feel that eating all this extra fat helps the body. As one wise doctor said to me "You know your diagnosis of Drusen in the eyes means that lipids are overflowing throughout all your body tissues, but you are only becoming aware of it because the doctors are only looking at your eyes." Hmmm.... something to think about.

Posted by: Michele B at May 16th, 2020 3:26 PM

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