[Neuroscience] Re: Carotenoid Transport into the RPE

John H. via neur-sci%40net.bio.net (by johnh from goawayplease.com)
Sun Dec 9 02:04:39 EST 2007


This also looks very promising, just came across it. NAC is a popular
antioxidant. There is a recent warning about it though but I can't find it.
However a very quick look suggests it shows promise as an adjunct treatment
across a wide range of pathologies.

Recent warning is below but it is hardly a serious one. Typical of the USA,
will do anything to attack the supplement industry. If NAC were such a
problem as outlined here it would have become obvious a long time ago. 
Possibly an issue for those with CHD, high blood pressure, or over 60 years 
of age but your doctor could probably monitor for this condition.

I can't explain this simply but degradation failure was precisely my target 
this afternoon, after a week thinking about it .... No point improving 
phagocytosis without degradation so as the authors note this represents a 
new strategy for AMD, and Stargardts for that matter.

: Klin Monatsbl Augenheilkd. 2007 Jul;224(7):580-4.Click here to read Links

[N-acetylcysteine improves lysosomal function and enhances the degradation 
of photoreceptor outer segments in cultured RPE cells]

[Article in German]

Schütt F, Völcker HE, Dithmar S.

Universitätsaugenklinik Heidelberg, Heidelberg

[N-acetylcysteine improves lysosomal function and enhances the degradation
of photoreceptor outer segments in cultured RPE cells]
[Article in German]

Universitätsaugenklinik Heidelberg, Heidelberg, Germany.

BACKGROUND: In the retinal pigment epithelium (RPE) lipofuscin granules
accumulate with age in the lysosomal compartment mainly as a byproduct of
constant phagocytosis of oxidized membranous discs shed from photoreceptor
outer segments. Antioxidative defiency and prooxidative conditions in the
RPE play a key role in the pathogenesis of RPE dysfunction and macular
degenerations such as ARMD. In human RPE cell cultures we investigated the
antioxidative effect of N-acetylcysteine (ACC) on lysosomal functions.
METHODS: Primary human RPE cell cultures were loaded with regular or
oxidized human and porcine rod outer segments (ROS) and treated with ACC.
Lysosomal volume and accumulation of autofluorescent material was measured
using [14C] methylamine accumulation and FACS analysis. The regulation
pattern of lysosomal proteins were investigated by proteome analysis.
RESULTS: ACC reduced total lysosomal volume in control, ROS and oxidized ROS
fed RPE cells. After ROS incubation increased accumulation of
autofluorescent material was measured. ACC treatment decreased intracellular
accumulation. Furthermore, incubation with ACC leads to a general down
regulation of lysosomal proteins. CONCLUSION: In our cell culture model of
ROS fed RPE cells simulating aged RPE ACC improves lysosomal volume and
metabolism. Therefore ACC may represent a new prophylactic and causal
treatment option for AMD.

PMID: 17657692 [PubMed - indexed for MEDLINE]

7/09/2007 13:22

A Type Of Antioxidant May Not Be As Safe As Once Thought

Certain preparations taken to enhance athletic performance or stave off
disease contain an antioxidant that could cause harm. According to new
research at the University of Virginia Health System, N-acetylcysteine
(NAC), an antioxidant commonly used in nutritional and body building
supplements, can form a red blood cell derived molecule that makes blood
vessels think they are not getting enough oxygen. This leads to pulmonary
arterial hypertension (PAH), a serious condition characterized by high blood
pressure in the arteries that carry blood to the lungs. The results appear
in the September issue of the Journal of Clinical Investigation.

"NAC fools the body into thinking that it has an oxygen shortage," said Dr.
Ben Gaston, UVa Children's Hospital pediatrician and researcher who led the
study. "We found that an NAC product formed by red blood cells, know as a
nitrosothiol, bypasses the normal regulation of oxygen sensing. It tells the
arteries in the lung to 'remodel'; they become narrow, increasing the blood
pressure in the lungs and causing the right side of the heart to swell."

Gaston notes that this is an entirely new understanding of the way oxygen is
sensed by the body. The body responds to nitrosothiols, which are made when
a decreased amount of oxygen is being carried by red blood cells; the
response is not to the amount of oxygen dissolved in blood. He says that
this pathway was designed much more elegantly than anyone had previously
imagined. "We were really surprised", he said.

The research team administered both NAC and nitrosothiols to mice for three
weeks. The NAC was converted by red blood cells into the nitrosothiol,
S-nitroso-N-acetylcysteine (SNOAC). The normal mice that received NAC and
SNOAC developed PAH. Mice missing an enzyme known as endothelial nitric
oxide synthase did not convert NAC to SNOAC, and were protected from the
adverse effects of NAC, but not SNOAC. This suggests that NAC must be
converted to SNOAC to cause PAH.

Could regular use of NAC produce the same effects in humans? The next step
is to determine a threshold past which antioxidant use becomes detrimental
to heart or lung function, according to Dr. Lisa Palmer, co-researcher of
the study.

"The more we understand about complexities in humans, the more we need to be
aware of chemical reactions in the body," said Palmer.

According to Gaston and Palmer, NAC is being tested in clinical trials for
patients with cystic fibrosis as well as other conditions; and clinical
trials with nitrosothiols are being planned. These results, Palmer says,
should motivate researchers to check their patients for PAH.

The results also open up a range of possibilities in treating PAH. Palmer
added that the signaling process could be restorative and healing if they
figured out how to keep NAC from fooling the body.

"From here we could devise new ways for sensing hypoxia or we could in
theory modify signaling to treat PAH," Palmer said.

"Don W" <dwilgus from prodigy.net> wrote in message
news:5855eec2-216d-4e70-986d-4aeaf8d63d1c from p69g2000hsa.googlegroups.com...
> John,
>  Since I am at the AR end of ARMD I cannot comment too much on the
> Stargardt's problem.  Except to say that I think your efforts are
> quite noble to help that 11 year old.  I can only imagine the impact
> on the parents.  Good luck with your efforts.
>  That small study on zinc and drusen appeared in Exp Eye Res 2007 Apr
> by Lengyel, as you probably know.
>  Oh, have not read (or heard of) the "reduction of total drusen" by
> the "folk wisdom" approach (blueblockers).  The reduction part threw
> me.  Where did you pick that up?
>  One side effect of this thread is it has given me a better heads up
> on the biophysics of the whole (hole??) darn problem.  Thanks.
> Don W.

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