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Eye drops are expected to cure cataracts

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2018/09/28 17:23
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In early tests, a compound called sterol increased lens transparency
 
American researchers have discovered a molecule that binds to misfolded proteins in the eye, allowing it to redissolve. This sterol molecule demonstrates the potential for non-surgical treatment of cataracts - the ophthalmic solution containing this substance partially reverses the cataract in mice and restores partial transparency to the isolated human lens.
 
Currently, patients with cataracts must undergo surgery to restore vision. This is a relatively simple approach in developed regions, but Jason Gestwicki, the project's leader at the University of California at San Francisco, said, "There are currently about 100 million cataract patients in the world who are unable to undergo surgery. It becomes a blind person. It can guarantee the effect for a long time, and only the least trained local treatment method is exactly what we need."
 
Cataract is caused by damage to the lens protein in the lens of the eye. These proteins are initially soluble and transparent, but they are never replaced and may fold incorrectly over time, resulting in very stable opaque, insoluble masses. "If we can find a small molecule that binds to a soluble, naturally folded lens protein, and the free energy of the binding reaction makes this state more stable... then we can basically reverse the aging of the lens protein. Process," Gestwicki explained.
 
Thermal screening
 
But so far, drugs that bind to the target protein are difficult to screen. "The lens protein has no enzyme function and only plays a structural role, so all the traditional methods of finding molecules that can bind to it are ineffective," Gestwicki said. To overcome this difficulty, the Gestwicki team developed a new high-throughput screening technique that measures the effect of different molecules on the melting of alpha and beta lens proteins in misfolded morphology. Since the misfolded morphology is more heat resistant, a decrease in melting point means that the lens has changed to its original form.
 
This screening method has found many molecules that reduce the melting point of the lens protein - mainly sterols. 5-cholestene-3b,25-diol is one of the most promising and can lower the melting point by 2 °C. Further testing, including nuclear magnetic resonance experiments, showed that this molecule links the alpha and beta lens proteins together to form a dimer. The team speculated that this may stabilize the lens protein and not only prevent the formation of misfolded, insoluble states, but does reverse the process.
 
The team tested steroid-containing eye drops on isolated cataractous human lenses and live mice with cataracts by genetic engineering. "We did see promising advances in lens transparency and protein solubility... although not completely reversed," Gestwicki said. Most mice, for example, the degree of cataract measured by the LOCS III system, are classified into one to five grades according to the turbidity of the lens, and six eye drops are used in one cycle per week to reduce the turbidity by at least one grade. . It’s still not possible to measure its impact on vision, Gestwicki said, because mice rely on the sense of smell to “see” the world – the next step is to do more experiments on animals, such as dogs, to better understand This eye drops improve vision.
 
Early
 
“These are early studies, and there is still a lot of work to do. But in this direction, after 5 or 10 years, you may be able to develop a drug that can delay the process and even reverse the early senile cataract.” J Fielding Hejtmancik, who studies the genetics of eye diseases, said the US Institutes of Health. “They have done some pretty good work and explained that their active substances can both block protein denaturation and dissolve amyloid fibers.” However, he does not believe that sterols can reverse very late cataracts. "I suspect that using these agents to reverse early polymerization may be feasible. It was basically just protein aggregation. If you sit back and watch for years, they will form covalent crosslinks and then you won't be able to dissolve them." ”
 
Gestwicki and colleagues set up a university-derived company to develop their technology and hopefully find a way to be effective for large mammals within a few years.
 
Hejtmancik said that if they can prove that their compounds are effective, the prospect of developing a therapeutic eye drops looks good. “These sterols may be relatively cheap and probably non-toxic,” he said. “But they are not the only ones doing this kind of research – it's an increasingly competitive field.”
 
(Jilin Qijian Biotechnology Co., Ltd._Biopharmaceutical _ www.qjbio.com.cn)