Multi-parametric MRI of the physiology and optics of the in-vivo mouse lens.

Abstract

The optics of the ocular lens are determined by its geometry (shape and volume) and its inherent gradient of refractive index (water to protein ratio), which are in turn maintained by unique cellular physiology known as the lens internal microcirculation system. Previously, magnetic resonance imaging (MRI) has been used on ex vivo organ cultured bovine lenses to show that pharmacological perturbations to this microcirculation system disrupt ionic and fluid homeostasis and overall lens optics. In this study, we have optimised in vivo MRI protocols for use on wild-type and transgenic mouse models so that the effects of genetically perturbing the lens microcirculation system on lens properties can be studied. In vivo MRI protocols and post-analysis methods for studying the mouse lens were optimised and used to measure the lens geometry, diffusion, T1 and T2, as well as the refractive index (n) calculated from T2, in wild-type mice and the genetically modified Cx50KI46 mouse. In this animal line, gap junctional coupling in the lens is increased by knocking in the gap junction protein Cx46 into the Cx50 locus. Relative to wild-type mice, Cx50KI46 mice showed significantly reduced lens size and radius of curvature, increased T1 and T2 values, and decreased n in the lens nucleus, which was consistent with the developmental and functional changes characterised previously in this lens model. These proof of principle experiments show that in vivo MRI can be applied to transgenic mouse models to gain mechanistic insights into the relationship between lens physiology and optics, and in the future suggest that longitudinal studies can be performed to determine how this relationship is altered by age in mouse models of cataract.