Abstract
Purpose :
The absence of clinical tools to evaluate individual variation in the pace of aging and responses to diabetic hyperglycemia represent major impediments to understanding aging, evaluating diabetic complications, and maximizing health throughout life. The lens is an ideal tissue for quantitative assessment of molecular events associated with aging and diabetes in vivo. Long-lived proteins in lens fiber cells are expressed during fetal life, do not undergo turnover, and accumulate post-translational alterations throughout life. Quasi-elastic light scattering (QLS) is a non-invasive technique for quantitative assessment of molecular changes in the lens in vivo. This study is designed to longitudinally measure both age- and glycemia-dependent QLS signals in vivo in lenses of living C57BL/6 mice as a function of advancing age and in response to chemically-induced diabetes mellitus (DM). We hypothesized that cumulative alterations in lens proteins may constitute an in vivo biomarker of molecular aging, and that the rate of these changes will be accelerated by chronic diabetic hyperglycemia.
Methods :
Quasi-elastic light scattering (QLS) was used to measure: (i) longitudinal age-dependent changes in vivo in lenses of unanesthetized C57BL/6 mice aged 4–18 months, and (ii) longitudinal glycemia-dependent changes in lenses of unanesthetized C57BL/6 mice aged 4–10 months treated with streptozotocin (STZ), a model of type-1 diabetes. Concomitant retinal damage was assessed in using electroretinography and postmortem immunofluorescence staining.
Results :
Our results indicated that QLS metrics can be acquired noninvasively in unanesthetized mice and human subjects with diabetes. Both static and dynamic light scattering metrics were significantly altered in lenses of mice with diabetes compared to controls.
Conclusions :
Our findings demonstrate that QLS analysis of lens proteins provides a practical technique for noninvasive assessment of molecular aging and long-term glycemic status in vivo. We are also conducting a companion cross-sectional clinical validation study in human subjects with type 1 DM.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.