Age-related Stiffening Of Human Lens Is The Result Of A Variation In Spatial Distribution Of Lens Elastic Modulus

Abstract

Purpose: : The loss of accommodation power is believed to be primarily caused by an age-related increase of the stiffness of the crystalline lens. However, in-depth characterizations of the stiffening processin the aging lens have been so far prevented by the lack of suitable mechanical testing methods. Using novel Brillouin microscopy, which enables non-contact spatially-resolved measurements of elastic modulus, we characterized age-related stiffening of the lens by measuring the spatial distribution of lens elastic modulus and its age variation.

Methods: : Brillouin light scattering inside the lens involves a spectral shift proportional to the longitudinal modulus of elasticity of the tissue. With a single-frequency laser and a home-built ultrahigh-resolution spectrometer we measured the Brillouin frequency shift. Using confocal scanning, we mapped Brillouin elastic modulus of 14 pairs of human lenses ex vivo from cadaver eyes ranging between 23 and 67 yr-old.

Results: : From the Brillouin measurement of the spatial distribution of elastic modulus, we extracted several elasticity quantitative measures to characterize lens stiffness as a function of age. Overall lens stiffness was measured to strongly depend on age progression (R²>0.85). Maximum modulus (in the nucleus) and minimum modulus (in the cortex) did not show statistically significant agedependency; on the other hand, parameters involving the spatial distribution of modulus (e.g. equivalent modulus, maximum modulus plateau, elasticity gradient), which determine global lens stiffness, were measured to have high correlation with age (R²>0.9).

Conclusions: : The Brillouin measurement indicates that the overall lens stiffness increases with age as a result of a variation in the spatial distribution of the elastic modulus inside the aging lens. While maximum and minimum values for the modulus do not vary with age, the increase of spatial gradient of elasticity from cortex to nucleus and of the spatial extent of maximum modulus are responsible for the overall stiffening effect. These results provide novel insights into the mechanism of accommodation and demonstrate the great potential of three-dimensional measurements of lens mechanical properties enabled by Brillouin microscopy.

Keywords: accommodation • imaging methods (CT, FA, ICG, MRI, OCT, RTA, SLO, ultrasound) • presbyopia