Molecular Interactions Keep Vision Clear
Researchers have uncovered a key molecular interaction that affects the clarity of the lens in the eye and that may play a role in the formation of cataracts, a clouding of the lens that can lead to blindness. The results may eventually lead to cataract treatments that do not involve surgically replacing the lens.
Researchers have discovered that a weak attraction between two of the three crystallins that make up the lens in the eyes of mammals keeps the lens transparent, as shown in this 3-D model (left) and in slices from that model (right). No attraction (top) between the alpha (red spheres) and gamma (blue spheres) crystallins leads to disaggregation of the colloid structure and a loss of transparency. Weak attraction (middle) ensures that the crystallins are dispersed properly, rendering the structure transparent, whereas strong attraction (bottom) also creates strong fluctuations in the density, reducing transparency.
In mammals, the lens is composed of three main classes of proteins: α-, β- and γ-crystallin. In a normal lens, these proteins are dense and highly ordered, which makes them transparent and refractive. As the lenses age and are exposed to UV light, the proteins can aggregate or phase separate, causing them to become opaque.
According to Giuseppe Foffi of the Ecole Polytechnique Fédérale de Lausanne (EPFL) and of the Institut Romand de Recherche Numérique en Physique des Matériaux in Switzerland, cataracts are such a common problem worldwide that many scientists have focused their energy on understanding the causes. “Most of this work, however, focused on one protein at a time and often at low concentrations,” he explained. “In our work, we studied two of the three proteins at concentrations similar to those found in vivo.”
Foffi and fellow researchers from the University of Fribourg in Switzerland, the EPFL and the Rochester Institute of Technology in New York systematically studied the interactions between α-crystallin and γβ-crystallin (a form of γ-crystallin) in various concentrations and at various temperatures. The studies at the Paul Scherrer Institut in Villigen, Switzerland, included theoretical modeling accompanied by experiments using small-angle neutron scattering.
The scientists conducted extensive computer simulations designed to help them explain the experimental results. “To model the interactions, we started by assuming no attraction between the two species [α- and γβ-crystallin], but the results were frustrating,” he said. “No matter how we tried, we could not reproduce the experimental data.”
They then decided to take into account a possible interspecies attraction. They discovered that a small attraction between the α- and γβ-crystallin proteins plays a vital role in the stability of the solution. If it is too weak or too strong, the proteins aggregate, and this ultimately results in a loss of transparency.
Foffi said that the nature of the attraction and the protein interactions is not well understood. In general, a combination of hydrophobicity and electrostatics contributes to such interactions. However, on the surface of the proteins, the charge and the hydrophobic areas are not uniformly distributed. Instead, they create a “complex mosaic.”
“For the moment, the origin of the weak stabilizing attraction that we discovered is unclear,” he added. In the experiments, the two proteins have slightly opposite charges, which is compatible with attraction. However, the investigators do not know if this is the only source of attraction. They hope that scientists with different backgrounds will tackle this problem.
From here, Foffi said that the research is progressing in several directions. Already the group has begun experiments on the same system, varying the salt concentration of the buffer solution in which the proteins are maintained. It also is working to improve its computer modeling and plans to add the third protein.
“We hope that soon we will be able to perform experiments and simulations for the full ternary protein mixture that is responsible for eye-lens transparency,” he added.
Physical Review Letters, 2007, Vol. 99, 198103.
- A transparent optical component consisting of one or more pieces of optical glass with surfaces so curved (usually spherical) that they serve to converge or diverge the transmitted rays from an object, thus forming a real or virtual image of that object.
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