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Matthew Aaron Reilly, Wade Rich, TC Brandt, Nicholas Pennza, Zhuo Chen, Diego Valenzuela; A quantitative theory linking molecular-level events to changes in lens biomechanical and optical properties. Invest. Ophthalmol. Vis. Sci. 2021;62(8):2090.
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© ARVO (1962-2015); The Authors (2016-present)
Age-related changes in the optical and biomechanical properties of the lens cause presbyopia. However, the molecular origins of these changes remain unknown. In this study, experimental and computational approaches were combined to offer a mechanistic theory of age-related changes in lens material properties.
Fresh porcine lenses were characterized intact using digital photography and lens compression to determine their macroscopic optical and biomechanical properties. Lenses were then homogenized and fractionated, allowing further characterization using Raman spectroscopy (RS), dynamic light scattering (DLS), and dynamic shear rheometry (DSR). Experiments were conducted at 50°C to simulate “biochemical aging.” The resulting data were used to calibrate a biochemical computational model of lens aging. This model simulated the kinetics of biochemical changes in the lens while predicting changes in optical and mechanical properties.
RS indicated the thermal stability of lens proteins up to ~57°C, suggesting that incubation at 50°C may be a reasonable model for acceleration of biochemical kinetics in the lens. RS, DLS, and DSR measurements suggest that protein structural modifications precede aggregation, which in turn precedes changes in viscoelastic properties of lens protein solutions. At the macroscopic level, lens stiffening occurred at timescales very similar to those found using DSR. Changes to lens transparency occurred later in the process. Multi-scale modeling of these changes demonstrate the feasibility of protein unfolding leading to aggregation, then binding to the lens’ cytoskeleton. This could effectively reinforce the cytoskeleton by decreasing the mobility of its proteins.
While it is unknown whether thermosetting pig lenses recapitulates physiological aging mechanisms, this study offers the first mechanistic theory linking biochemical events to biomechanical and optical changes in lens material properties. Similarities between the ultimate material properties of intact lenses, homogenized lenses, and fractionated homogenates suggest that the simple experimental and theoretical models may capture the key aspects of age-related changes in lens material properties. Future work will require experiments using human donor lenses to ascertain the utility of both the experimental and theoretical models in understanding aging in the human lens.
This is a 2021 ARVO Annual Meeting abstract.
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