Om1975, thanks for your post. MsrA is one of several approaches that could be used to restore the lost chaperone activity of alpha-crystallin. It would help when the loss is due to oxidation. B ....
Om1975, thanks for your post. MsrA is one of several approaches that could be used to restore the lost chaperone activity of alpha-crystallin. It would help when the loss is due to oxidation. But loss of viability of alpha-crystallin is due to more than just oxidation. More than oxidation, I think the major loss is due to the cross-linking of alpha-crystallin with yellow or brown AGEs (Advanced Glycation End-Products) within the lens nucleus. These AGEs prevent alpha-crystallin from doing its job of preventing aggregation of beta- and gamma- crystallin. This picture is further complicated by the fact that the damaged AGE-crystallin complexes are trapped inside 'molecular mini-cages' formed by disulfide bonds between glutathione molecules. Thus to restore optical clarity, we must first smash open the glutathione mini-cages, and then use an AGE-crystallin cross-link breaker to recover the crystallin from the AGEs. Finally, the AGEs need to be washed out of the lens fibers, and the crystallin needs to be 'refolded'. How are we going to do all that? Well, the mini-cages can be broken by alpha-lipoic acid choline ester eyedrops (bought up by Novartis, now unavailable). Then, the AGE crosslinks can be broken by an AGE crosslink breaker such as phenacyl thiazolium bromide (PTB). In 2008, at the University of Arkansas, it was proven (in the lab) that this step alone partially restored the chaperone activity of alpha-crystallin. I don't know how to wash the AGEs out of the lens, however many of them are water-soluble. Finally, the misfolded crystallin can be refolded by lanosterol or another sterol. Maybe you know that lanosterol will soon be clinically trialed on cataract patients. But as you can see, it is unlikely to address the more important problems - namely, the mini-cages, the AGE-crystallin crosslinks, or the oxidation of methionine units in the crystallin for that matter.
But is it not amazing??? Today, from the research of chemists and biochemists, we know all of this and have ALL the tools at our disposal to cure this damn affliction without surgery. And does the eye profession know, or care? NO. NO. NO.
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