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Paul J Donaldson, Ehsan Vaghefi; Solute delivery to the core of the bovine lens is driven by the lens circulation system.. Invest. Ophthalmol. Vis. Sci. 2016;57(12):No Pagination Specified. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
To utilize T1-weight magnetic resonance imaging (MRI) of contrast agent penetration into the lens to test the hypothesis that the lens microcirculation system delivers solutes to the lens core faster than would occur by passive diffusion alone.
A lens of a pair of bovine lenses was organ cultured in Artificial Aqueous Humor (AAH), while the other lens was cultured in either AAH-High-K+, or AAH + 0.1mM Ouabain for 4 hours, in the presence of MRI contrast agents of varying molecular size (GadoSpinD, 17,000g/mol; GadospinF, 1,300g/mol; FeraSpinFS, 10nm). The time course of contrast agent penetration into the lens in the different culture conditions was visualised by T1-weighted imaging utilising a 4.7T high-field small animal magnet1. Penetration rates of reagents were extracted and compared to rates of passive diffusion calculated by a 1D model of diffusion.
Penetration of all contrast agents in the outer cortex of the lens was observed in lenses incubated in AAH, but only the lower molecular weight tracers (GadoSpinF and FeraSpinXS) were detected in the core of the lens. The pattern of GadoSpinF and FeraSpinXS penetration revealed two regions of contrast enhancement in the outer cortex and core, which were separated by a zone in the inner cortex from which the delivery of the contrast agents was restricted. The rate of delivery of GadospinF and FeraSpinXS to the core of the lens was calculated to be significantly faster by a factor of 8 than what could be achieved by passive diffusion alone. Furthermore the delivery of GadospinF and FeraSpinXS was abolished by the incubation of lenses in the presence of AAH-High-K+ or AAH + 0.1mM Ouabain, two conditions that are known to inhibit the lens circulation system by depolarising the lens potential and blocking the Na+ pump, respectively.
Our results show that the lens circulation system delivers small solutes to the lens core at a rate that is faster than would be predicted by passive diffusion alone. The extracellular pathway used to delivery solutes to the core appears to be associated with the sutures and exhibits a size selectivity that restricts the delivery of large molecules to the core. Our results support earlier work that shows an extracellular diffusion barrier exists in the inner cortex that divides the lens into two compartments.(1) Vaghefi et al. Am J Physiol Regul Integr Comp Physiol, 302: R1250–1259, 2012.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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