  Cataract is one of the most prevalent protein aggregation disorders and still
the biggest cause of vision loss worldwide. The human lens, in its core region,
lacks turnover of any cells or cellular components; it has therefore evolved
remarkable mechanisms for resisting protein aggregation for a lifetime. We now
report that one such mechanism relies on an unusually abundant metabolite,
myo-inositol, to suppress light-scattering aggregation of lens proteins. We
quantified aggregation suppression by in vitro turbidimetry and characterized
both macroscopic and microscopic mechanisms of myo-inositol action using
negative-stain electron microscopy, differential scanning fluorometry, and a
thermal scanning Raman spectroscopy apparatus. Given recent metabolomic
evidence that it is dramatically depleted in human cataractous lenses compared
to age-matched controls, we suggest that maintaining or restoring healthy
levels of myo-inositol in the lens may be a simple, safe, and widely available
strategy for reducing the global burden of cataract.
