Aβ-INDEPENDENT AND Aβ-POTENTIATED AGE-RELATED CHANGES IN THE LENS OF WILD-TYPE AND ALZHEIMER’S DISEASE TG2576 MICE

Abstract

We previously discovered that Aβ accumulates in the supranuclear region of the lens in the eyes of people with Alzheimer's Disease (AD) (Goldstein, Lancet, 2003) and Down Syndrome (DS; (Moncaster, PloS One, 2010). Aβ interacts with crystallin proteins in the lens to create light scattering aggregates. Crystallins comprise ∼90% of lens protein in mature lens fiber cells and undergo various post-translational modifications during aging that disrupt the normal functioning of the proteins, facilitating aggregation, insolubilization and light scattering. Here, we expand on previous work by us and others and investigated the aging effect of crystallins in an Aβ-independent and Aβ-potentiated environment and the effect on light scattering in lenses from aged (27 months) wild-type and Alzheimer's disease transgenic mice (Tg2576). Mice were bred, maintained and genotyped at Boston University. Mice were sacrificed at 27 months of age, perfused with phosphate buffer saline, lenses were isolated and then imaged under two different sources of light using a D70 digital Nikon camera and a custom-adapted Zeiss stereophotomicroscope. Wild-type aged mice demonstrated increased light scattering in two distinct concentric layers (cortical and outer nuclear) in the lens compared to young mice. Furthermore, Tg2576 aged mice showed increased scattering in the cortical layer compared to wild-type aged mice. Two distinct light scattering layers of the lens are affected during aging involving Aβ-potentiated mechanisms in Tg2576 mice and Aβ-independent mechanisms in wild-type mice.