Monitoring Molecular Aging of Lens Proteins using Quasi-Elastic Light Scattering

Abstract

Purpose : The absence of clinical tools to evaluate individual variation in the pace of aging represents a major impediment to understanding aging and maximizing health throughout life. Here, we demonstrate that the human lens is an ideal tissue for quantitative assessment of molecular aging in vivo. Crystallin proteins comprise ~90% of lens protein in mature lens fiber cells, do not undergo turnover, and remain extant throughout life. Crystallins undergo various post-translational modifications during aging. We hypothesize that cumulative alterations in the lens may constitute an in vivo biomarker of molecular aging for the human body.

Methods : Quasi-elastic light scattering (QLS) has been used to study the aggregation of lens proteins. Here we use QLS to measure changes in human lens proteins as a function of time in vitro and aging in vivo. We investigated changes in light scattering in vivo from the lenses of 34 healthy human subjects without history of eye disease (18 males, 16 females; ages 5-61). Measurements were acquired in the nucleus along the optical axis at a predetermined distance from the anterior capsule of the lens. Next, we examined time-dependent effects of in situ oxidation on QLS signals obtained from water-soluble human lens protein extract (hLPE) during long-term incubation in vitro.

Results : Clinical results indicated that aging-related QLS metrics can be acquired noninvasively in human subjects. Age-dependent QLS signal changes detected in vivo recapitulated time-dependent changes in hydrodynamic radius, protein polydispersity, and supramolecular order of human lens proteins during long-term incubation (~1 year) and in response to sustained oxidation (~2.5 months) in vitro.

Conclusions : Our findings demonstrate that QLS analysis of human lens proteins provides a practical technique and quantitative biomarker for objective assessment of molecular aging in vivo.

This is a 2020 ARVO Annual Meeting abstract.