How protein aggregations and lens fiber disorder result in nuclear and cortical cataracts

Commonly, lens opacities and cataract are considered protein aggregation disorders. Increased light scattering is attributed to larger high-molecular-weight fractions of proteins. The impact on transparency of fiber membranes and their age- and disease-related changes is addressed to a lesser extent in the literature. In the lens cortex of transparent human lenses, the lens fiber membranes have high refractive indexes compared with the cytoplasm, whereas there is almost no difference in the refractive indexes of membranes and cytoplasm in the lens nucleus. Therefore, in the lens cortex, transparency is obtained by a high spatial order of the lens fiber lattice to compensate for light scattering caused by differences of the refractive indexes. Any disturbance of the ordered lens fiber architecture in the cortex results in light scattering. In typical nuclear cataract, there is no major fiber disruption or extracellular debris to explain the opacity. The strong implication is that local fluctuations in crystallin density, due to the formation of insoluble aggregates, are the major cause of nuclear opacification. These fluctuations in density and refractive index, are considered to produce significant light scattering.