A native chemical chaperone in the human eye lens

TL;DR

This study identifies myo-inositol as a natural chemical chaperone in the human eye lens that suppresses protein aggregation, offering a potential strategy for cataract prevention by maintaining or restoring its levels.

Contribution

It reveals myo-inositol's role as a native chemical chaperone in the lens and suggests its depletion is linked to cataract formation, proposing a new preventive approach.

Findings

Myo-inositol suppresses lens protein aggregation in vitro.

Depletion of myo-inositol is observed in cataractous lenses.

Restoring myo-inositol levels may prevent or delay cataracts.

Abstract

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.