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The lens of the human eye is exquisitely adaptable, effortlessly producing sharp images of objects at different distances for most of our lives. However, it has long been a mystery as to how such optical precision is attained by biological growth processes.
“To perform such a demanding task, the lens must be built precisely, must remain transparent throughout life, and must be flexible enough,” explains Hrvoje Šikić, a mathematician at the University of Zagreb and coordinator of the EU-funded MOLEGRO project. “It grows throughout life but the rules that govern the growth of tissues and organs are not well understood in any biological system.”
The MOLEGRO team set out to develop a new mathematical model of the growth of the lens in mice as a step towards a similar model for the human lens. It was a joint endeavour between Šikić and Steven Bassnett from the School of Medicine at Washington University in Missouri.
Two ‘pedals’
Bassnett had been working on the physiology of the lens for many years but Šikić was able to bring a mathematician’s insights and skills to understand how the growth and function of the lens could be understood by modelling the behaviour of individual cells. “The hope was that by understanding lens growth from the mathematical point of view we could actually have a good understanding of the process,” he says.
The researchers chose to model a mouse lens, which had already been well studied, and ran many computer simulations of its growth throughout the rodent’s entire life.
To their surprise, Šikić and Bassnett found that the growth of the lens depends on only two variables, the ‘footprint’ area of each cell and the rate of division in each of four zones within the outer skin of the lens. This so-called ‘two-pedal’ model is able to replicate the growth of the entire lens over the lifetime of the mouse.
This also explains how an essentially random cell-division process is able to grow a lens to the correct shape with a tolerance of better than 1 %.
Cataract formation
The growth and movement of cells revealed by the model can also account for the appearance of cataracts in old age. One of the risk factors concerning cataract development is exposure to sunlight. Šikić speculates that the ultraviolet component of sunlight may cause mutations in lens cells which eventually lead to clouding of the tissue.
However, while mutations can occur at any time, the zonal structure of the model shows how mutated cells may at first be hidden, only moving into the visible part of the lens in later life. Similar effects may explain why there are no recorded cases of cancer affecting the lens.
Now that MOLEGRO has finished, the researchers are seeking funding to extend the modelling work to the more complex human lens.
“If our hypotheses about the cataract development prove to be correct for human lenses too, then this may lead to methods to reduce the burden of the disease,” Šikić says. “This is still the main cause of blindness in underdeveloped countries.”
He says the model already explains how older lenses become stiffer and thus less able to adjust their focus, leading to presbyopia and the near-universal need for reading glasses as people reach middle age.
Šikić was funded by a Marie Curie fellowship that allowed him to travel to the US to work with the Washington University group. “For our collaboration, the Marie Curie grant was essential. It really did help us tremendously.”