Friday, November 09, 2007

Finally, How Cataract is Formed

Finally, How Cataract is Formed

Cataract surgery in which normal lenses are removed and replaced with artificial ones is performed to nearly 5 million people annually. Cataract is the world's leading cause of blindness.

Cataract causes the transparent lens crystalline proteins to clump together causing light to be scattered once it enters the eye lens, resulting in cloudy vision or blindness.

To understand what happens in a simple way, we should first delve into
some characters of proteins. Proteins are made of polypeptide chains which are formed by bound together amino acids(the human body building units).
The polypeptides may be similar or different, as well as the sequence of amino acids differs for every polypeptide chain, and all are genetically encoded.

There are various types of physico-chemical bonds that maintain a protein configuration, so as to perform its structural or functional role. The natural, biological conformation of a protein is referred to as its native state.

Proteins vary in their stability, but any protein can be denatured (converted to unfolded or altered state). Mild conditions of pH and temperature must be used for the lab isolation and storage of proteins.

Mild denaturation is progressive, producing partial unfolding, while fully denatured proteins are in a random coil with no recognizable structure (like when your cat unfold a ball of wool- and you may strike her). The consequences of denaturation are loss of biological activity, decreased solubility and inability to form crystals.

Denaturation occurs when the surrounding conditions are changed, it can be brought by extremes of pH and high temperature, by chaotropic ions(e.g. trichloroacetate), concentrated urea, and ionic detergents(e.g.sodium dodecyl sulphate).

In each case the denaturing conditions weaken the non-covalent bonds(atoms are only attracted at their surfaces), that maintain its native structure, and stabilize a different denatured structure. If these conditions are removed , the native conformation may reform, but denaturation may be irreversible (it often causes protein aggregation).

Proteins denatured to insolubility can be dissolved under the right conditions, e.g. the solubility of boiled egg white (denatured protein ) in a strong urea solution.

Eye Proteins:
The eye lens is made up of densely packed crystalline proteins, arranged in such a way that light in the visible wavelength range can pass through, but for a variety of reasons including UV radiation exposure and age, these proteins are clumped together causing Cataract.

Research of the 3 major crystalline proteins individually did not reveal the real cause of cataract, but researching the interaction between them was the clue to understand proteins aggregation, which is the cause of other diseases like Alzheimer's disease.

the interaction between proteins was elucidated by studying 2 of them. It was found that fine tuned combination of attraction and repulsion between the 2 proteins resulted in an arrangement that was transparent to visible light, there had to be a weak attraction between the proteins in order for the eye lens to be transparent. Cataract may form if this balance is disrupted.

Lens proteins were modeled as colloidal particles, and the research revealed that there was a very narrow window in which the protein solution remained stable, and this was a necessary condition for lens transparency.

What keeps the interactions between eye proteins in the optimal weak range, is it foods we eat, geography we live with, or life style?
Next days may bear the answer.

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