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Ehsan Vaghefi Rezaei, Andy Kim, Paul Donaldson; Linking the optical properties of the lens to its cellular physiology: a multimodal imaging and modelling approach. Invest. Ophthalmol. Vis. Sci. 2013;54(15):4048.
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© ARVO (1962-2015); The Authors (2016-present)
To determine the relationship between cellular physiology, circulating fluid fluxes, gradient of refractive index (GRIN), and the overall optical properties of the ocular lens at the tissue level.
Bovine lenses were organ cultured in Artificial Aqueous Humor (AAH) or either high extracellular potassium (KCl-AAH), or low temperature (Low T-AAH) to depolarize the lens potential, and to inhibit active transport, respectively. Water fluxes were imaged by real time heavy water (D2O) enhanced Proton Density MRI, while water/protein gradients were visualized using T2 MRI. Using existing formulas T2 maps were converted to 3D GRIN meshes that were then implemented in our ray-tracing software to establish the optical performance of lenses cultured in AAH, KCl-AAH and Low T-AAH. In parallel, we created a finite element model of lens’s circulating currents and simulated same perturbations, using appropriate boundary conditions.
MRI visualisation of D2O penetration into the lens revealed preferential inflow of water at both the anterior and posterior poles of the lens that was followed by circumferential movement towards the equator. These directed water fluxes were abolished in lens incubated in KCl-AAH and LOW T-AAH conditions. Our computational model also predicted that KCL-AAH and LOW T-AAH will result in 89% and 83% reduction of lens transmembrane electro-potential and 95% and 89% decrease of circulating fluxes, respectively. Furthermore, T2 MRI revealed that KCL-AAH resulted in water accumulation and GRIN reduction in the core of the lens. LOW T-AAH lenses’ exhibited a flattening of the GRIN profile due to increases values in the inner cortex. Optical modelling showed that changes in GRIN induced by incubating lenses in KCL-AAH and LOW T-AAH solutions led to a myopic shift of 1.3mm±0.47 and 7.9mm±0.74 respectively, that link the underlying physiology of the lens to it optical properties.
We have shown that spatial differences in transport processes at the cellular level generate fluid fluxes that actively remove water from the core of the lens. This circulation creates a radial water concentration gradient that establishes the GRIN that ultimately determines the optical properties of the lens at the tissue level. These distinct multi-scale processes can be captured by a 3D computer model that predicts the changes in optical properties of the lens.
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