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Matthew Aaron Reilly; Finite Element Analysis of Oxidative Stress-Induced Changes in the Mechanical Properties of the Lens. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):3567.
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© ARVO (1962-2015); The Authors (2016-present)
Age-related changes in lens mechanical properties have been implicated in the pathogenesis of presbyopia. Damage due to oxidative stress has been implicated in the pathogenesis of age-related nuclear cataract. The present study simulates the accumulation of oxidative damage to the lens with age and how this may result in age-related stiffening of the lens.
A mechanochemical finite element model of the human lens was constructed to simulate the effects of lens transport and biochemical reactions within the lens. Transport and regeneration of glutathione were simulated modeled. Denaturation and crosslinking of crystallins were also modeled. A constitutive model was developed relating crosslink density to elastic modulus. The model was used to simulate the effects of 60 years of aging on the lens’ modulus.
The modulus at the center of the lens increased slowly until age 35 after which it increased rapidly (Fig. 1). The modulus near the surface remained relatively constant throughout life.
The predictions of this model are in qualitative agreement with the elastic modulus distribution data of Wilde et al. (Exp. Eye Res. 97:36-48, 2012), suggesting that the change in lens properties could be due to oxidative crosslinking. The slow change in modulus with age in the young lens’ nucleus may be due to the relative abundance of native crystallins which are protected from crosslinking. The accumulation of denatured crystallins with age gives rise to an age-related exponential increase in the elastic modulus within the nucleus. Adding additional antioxidants (e.g. ascorbate) and steps to the crystalline denaturation pathway to the model further delays the onset of rapid lens stiffening in the model. Each of these effectively buffer against oxidative stress, thereby shifting the elbow in the curve further to the right on the aging axis.
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