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Senile cataracts - curable with presbyopia eyedrops
 
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Published: 3 years ago
 

Senile cataracts - curable with presbyopia eyedrops


When you have cataracts on the edges of the lens (cortical, PSC, anterior), the AGEs basically have disabled the Alpha crystallin so that it can no longer separate the tangled mess of other lens proteins.  I think this also includes diabetic cataracts.  If the cataracts are not too advanced, then NAC eyedrops like "Can-C" or "Brite Eyes" might break some of the connections between the AGEs and the Alpha crystallin.  If the cataracts are advanced, the best plan would be to have an AGE crosslink breaker eyedrop which would release the Alpha crystallin and restore its chaperone activity, although such an eyedrop does not exist.  At the same time, it would be a good idea to block further glycation of Alpha crystallin by AGEs using an anti-glycation eyedrop containing. for example, an aldose reductase inhibitor.  Anti-glycation eyedrops like this do exist, but only for dogs.  However, use of lanosterol eyedrops (Lanomax) might stimulate epithelial cells on the front surface of the lens to produce more Alpha crystallin, and start to reverse the cataract.  Fortunately, with the exception of PSCs on the back of the lens, cataracts on the edges of the lens are easy to reach with eyedrops, whatever you use - "Can-C", "Brite Eyes", or "Lanomax".

When you have cataracts in the nucleus of the lens (nuclear) (the most common kind, which includes mine), the picture is far more complicated.  Here, colored AGE's (pigments), and/or tryptophan metabolites like xanthurenic acid, have combined with alpha, beta and gamma crystallins.  The colored pigments cause the lens to absorb UVA radiation which it would not otherwise do. The absorption of UVA generates free radicals and singlet oxygen which cause further cross-linking between proteins, clouding the entire lens.  The lens uses glutathione to mop up the mess, but finally the glutathione itself becomes cross-linked via its own sulfur atoms.  So you end up with a mess of mixed disulfides with colored pigments trapped in the center - your classical nuclear cataract.  The obvious thing to do would be to attack the disulfide bonds and release the glutathione so that it can do its job. The bad news is, it is very difficult for any eyedrops to penetrate to the center of the lens. The good news is that, if an eyedrop could reach the center of the lens, these disulfide bonds could then be broken by reducing agents.  Examples are sodium borohydride, NaBH4 (highly toxic, no use to us), the sulfite preservatives in wine (probably toxic in eyedrop form), erythritol (a sugar alcohol artificial sweetener, already available in some eyedrops for dry eye), thioredoxin (TRx) and glutaredoxin (TTase) (not available in eyedrops, although they could be considered), and finally - alpha-lipoic acid. 

Like glutathione, alpha-lipoic acid is a sulfur-containing substance, and it may seem strange that we would dream of using yet another sulfur-containing molecule to clean up the mess.  But this works!  You see, the US company Encore Vision developed an eyedrop known as EV-06 containing alpha-lipoic acid and a choline ester.  Now this eyedrop was developed for presbyopia, not for cataract.  But presbyopia and nuclear cataract share similar features.  In presbyopia, the lens loses its elasticity and can no longer focus properly, due to disulfide bonds.  In nuclear cataract, AGEs, pigments and damaged proteins are trapped in the nucleus by those same disulfide bonds. 

What I'm saying is that EV-06 might well reverse senile nuclear cataract - better than "Can-C", better than "Brite Eyes", better than "Lanomax".  Encore Vision successfully completed phase 2 clinical trials of EV-06 for presbyopia in 2016.  

"In a Phase I/II masked, placebo-controlled proof-of-concept study, 50 patients were treated daily for 90 days with topical EV06 and 25 received a placebo. At day 90, 82% of the EV06-treated group had 20/40 near vision, and more than half demonstrated a gain of at least 10 letters in distance-corrected near visual acuity in the nondominant eye as well as bilateral vision.  Researchers had found that the lens loses flexibility when oxidation-induced disulphide bonds form between crystalline proteins, which inhibits accommodation, Burns reported at OIS@ASCRS 2016. EV06 interacts with enzymes within the lens fiber cells to chemically reduce lipoic acid and actively form dihydrolipoic acid, which in turn reduces the disulphide bonds and restores microfluidics to the lens".

There's only one little problem.  EV06 was bought by the Swiss pharmaceutical giant, Novartis, in January 2017. Novartis is now calling the EV06 drop UNR844.  It is now 2018, and Novartis has made no move to release these eyedrops.  

 

 
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