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Cataracts are the most common eye disease in humans. However, the exact processes leading to this condition are not fully understood. A team of researchers led by the Technical University of Munich (TUM) has now discovered that the composition of the protein solution plays a determining role. Their conclusions are contrary to the dominant opinion on the ground.
The lens cells are made up of a highly concentrated protein solution that is normally clear. “When the balance of proteins in the lens is destroyed, they clump together and the lens becomes cloudy,” explains Professor Johannes Buchner of the Chair of Biotechnology at TUM. This results in the disease known as cataracts.
Clouding can have different causes. Since lens proteins form in the embryo and are not replaced, damage can build up over the years, ultimately causing clouding of the lens. This is why cataracts mainly occur in the elderly. But some individuals have a genetic predisposition to eye disease, in which proteins in the lens of the eye mutate. In these cases, cataracts are present at birth or appear during childhood.
Unstable protein eliminated immediately
Scientists have studied strains of mice with hereditary cataracts. They worked with the research group surrounding Jochen Graw, an expert in eye lenses who, until 2019, was a professor at the Institute for Developmental Genetics at Helmholtz Zentrum München.
Until now, the mainstream has said that only defective proteins in the eye react with each other and form clumps. But Buchner’s team has now shown that, in mice with “genetic cataracts”, this is not the case. “We found that the mutated and unstable proteins in the lens were not there,” Buchner explains. “They are eliminated immediately.” Instead, “healthy” proteins clump together. “Our model, based on this new knowledge, says that the balance between different proteins, or their relationships between them, is important. When one of these components is missing, the others interact and form clumps.”
Important step in the treatment of cataracts
Many studies have been done to understand the causes of cataracts. “But never before has there been such a comprehensive survey of lenses in mice, comparing wild populations and mutants,” Buchner says. The new knowledge is an important step in the search for new methods of treating cataracts. The most common method is surgery, in which artificial lenses are implanted in the eye.
“If you understand exactly what’s going on, you can also think about ways to use drugs to disrupt bad interactions,” says Buchner. “But we have a long way to go – and first we have to show that the proposed model also applies to the lens of the human eye.”
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Publications:
Schmid, PWN, Lim, NCH, Peters, C. et al .: Imbalances in the lens proteome are linked to the formation of cataracts.
Nat Struct Mol Biol 28, 143-151 (2021).
More information:
Small-angle x-ray scattering (SAXS) measurements for the study were carried out by a research team led by Professor Tobias Madl of the Medical University of Graz.
Contact:
Teacher. Dr. Johannes Buchner
Technical University of Munich (TUM)
Department of Chemistry
Phone. +49 89 289 13340
[email protected]
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