Spatiotemporal changes in the human lens proteome: critical insights into long-lived proteins

Publication date: Available online 6 November 2019Source: Progress in Retinal and Eye ResearchAuthor(s): Kevin L. Schey, Zhen Wang, Michael Friedrich, Donita L. Garland, Roger J.W. TruscottAbstractThe ocular lens is a unique tissue that contains an age gradient of cells and proteins ranging from newly differentiated cells containing newly synthesized proteins to cells and proteins that are as old as the organism. Thus, the ocular lens is an excellent model for studying long-lived proteins (LLPs) and the effects of aging and post-translational modifications on protein structure and function. Given the architecture of the lens, with young fiber cells in the outer cortex and the oldest cells in the lens nucleus, spatially-resolved studies provide information on age-specific protein changes. In this review, experimental strategies and proteomic methods that have been used to examine age-related and cataract-specific changes to the human lens proteome are described. Measured spatio-temporal changes in the human lens proteome are summarized and reveal a highly consistent, time-dependent set of modifications observed in transparent human lenses. Such measurements have led to the discovery of cataract-specific modifications and the realization that many animal systems are unsuitable to study many of these modifications. Mechanisms of protein modifications such as deamidation, racemization, truncation, and protein-protein crosslinking are presented and the implications of such mechani...
Source: Progress in Retinal and Eye Research - Category: Opthalmology Source Type: research