Within the lens, water can be classed as being either protein-bound or free. The interactions between water and protein define which conformational state proteins will adopt
27 and are thus considered integral for proteins to maintain their refractive index increment. Given the importance of water in protein structure and function, an imbalance in the steady-state bound and free water proportions within the lens would be expected to produce downstream effects on the refractive properties of the lens. Indeed, a progressive increase in the ratio of free-to-bound water has been observed to occur with age,
28–30 and this has been correlated to a concurrent decrease in the refractive index of the lens, especially in the nucleus.
19,20,24 Alterations in lens hydration state have also been implicated in the loss of transparency of the lens. Cataractous lenses have been found to contain higher amounts of free water compared to clear lenses,
30,31 and an increased movement of water from a bound to a free state in opaque compared to transparent regions of the same lens has also been reported.
32,33 Furthermore, the lens has been shown to, at steady-state, actively maintain a gradient of free water concentration such that it is highest in the cortex relative to the nucleus.
34–36 Our laboratory has previously demonstrated through a series of studies on organ-cultured bovine lenses that pharmacologically dissipating the inherent free water gradient had the effect of altering the lens optical properties,
37 raising the question whether a similar redistribution of the steady-state free and bound water gradients occurs with aging in the human lens. Finally, there has also been speculation about an overall dehydration (i.e., loss of total water consisting of both free and bound components) of the lens with age; however, the existing literature is incomplete and contradictory. Although most studies report a relative dehydration of the lens with age,
30,31,38,39 others have reported that lens total water content does not change
29,40,41 or even increases with age.
42 It should also be noted that majority of the investigations into the various aspects of lens hydration to date have been performed on isolated ex vivo human lenses using destructive methods.