Protein posttranslational modification (PTM) by glycation: Role in lens aging and age-related cataractogenesis

Xingjun Fan, Vincent M. Monnier

Research output: Contribution to journalArticlepeer-review

Abstract

Crystallins, the most prevalent lens proteins, have no turnover throughout the entire human lifespan. These long-lived proteins are susceptible to post-synthetic modifications, including oxidation and glycation, which are believed to be some of the primary mechanisms for age-related cataractogenesis. Thanks to high glutathione (GSH) and ascorbic acid (ASA) levels as well as low oxygen content, the human lens is able to maintain its transparency for several decades. Aging accumulates substantial changes in the human lens, including a decreased glutathione concentration, increased reactive oxygen species (ROS) formation, impaired antioxidative defense capacity, and increased redox-active metal ions, which induce glucose and ascorbic acid degradation and protein glycation. The glycated lens crystallins are either prone to UVA mediated free radical production or they attract metal ion binding, which can trigger additional protein oxidation and modification. This vicious cycle is expected to be exacerbated with older age or diabetic conditions. ASA serves as an antioxidant in the human lens under reducing conditions to protect the human lens from damage, but ASA converts to the pro-oxidative role and causes lens protein damage by ascorbylation in high oxidation or enriched redox-active metal ion conditions. This review is dedicated in honor of Dr. Frank Giblin, a great friend and superb scientist, whose pioneering and relentless work over the past 45 years has provided critical insight into lens redox regulation and glutathione homeostasis during aging and cataractogenesis.

Original languageEnglish (US)
Article number108705
JournalExperimental eye research
Volume210
DOIs
StatePublished - Sep 2021
Externally publishedYes

Keywords

  • Aging
  • Ascorbic acid
  • Cataractogenesis
  • Cataracts
  • Glycation
  • Oxidation
  • Protein aggregation
  • Protein posttranslational modification

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

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