Antioxidant delivery to the lens nucleus: A strategy to delay age related nuclear cataract

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Abstract

Age related nuclear (ARN) cataract is associated with the accumulative effects of oxidative damage to proteins in the lens nucleus. Since it is preceded by a loss of the key lens antioxidant GSH specifically in the lens centre, but not the lens periphery or cortex, ARN cataract is thought to be due to a failure to deliver GSH to the nucleus. Due to its large size, the avascular lens cannot rely on passive diffusion alone to deliver GSH to deeper lying fiber cells. Instead it has been proposed that the lens operates an internal microcirculation system which delivers nutrients to the lens nucleus faster than would occur by passive diffusion alone. Consistent with this model, our group has used MRI and confocal microscopy to visualize this microcirculation and have revealed that the lens sutures serve as an extracellular pathway to deliver molecules to the lens nucleus. Furthermore, we have shown that cells in the nucleus express transporters that are potentially capable of accumulating the GSH and glucose convected to them via the microcirculation system. These results suggest that harnessing the circulation system to deliver antioxidants to the lens nucleus is a potential strategy to delay the onset of ARN cataract.

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