ArticleScience advances2024
Prevention of age-related truncation of γ-glutamylcysteine ligase catalytic subunit (GCLC) delays cataract formation.
Article in Science advances, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 12 citations in OpenAlex.
- Cataract GWAS meta-analysis and multi-omics Mendelian randomisation inform disease mechanisms and candidate target prioritisation.EBioMedicine · 2026Article
- RORA Targeting PRNP Modulates Age-Related Cataract via Activation Oxidative Injury-Induced Cellular Senescence and Apoptosis of Lens Epithelial Cells.Aging cell · 2026Article
- Kaempferol suppresses fibroblast-like synoviocyte proliferation in rheumatoid arthritis by targeting glutamate-cysteine ligase modifier subunit to inhibit ferroptosis resistance.Bone & joint research · 2026Article
- Lens aging and disease: Molecular mechanisms, functional consequences, and pharmacological implications.Progress in retinal and eye research · 2026Review
- Fullerenol Eye Drops Mitigate UVB-Induced Cataract Progression by Inhibiting Oxidative Stress and Cellular Senescence.Antioxidants (Basel, Switzerland) · 2026Article
- Article
- Dominant spinal muscular atrophy linked mutations in the cargo binding domain of BICD2 result in altered interactomes and dynein hyperactivity.bioRxiv : the preprint server for biology · 2025Article
- Cyclic cell-penetrating peptide-engineered ceria nanoparticles for non-invasive alleviation of ultraviolet radiation-induced cataract.Journal of nanobiotechnology · 2025Article
- Oxidative Stress in Cataract Formation: Is There a Treatment Approach on the Horizon?Antioxidants (Basel, Switzerland) · 2024Review
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
A sharp drop in lenticular glutathione (GSH) plays a pivotal role in age-related cataract (ARC) formation. Despite recognizing GSH's importance in lens defense for decades, its decline with age remains puzzling. Our recent study revealed an age-related truncation affecting the essential GSH biosynthesis enzyme, the γ-glutamylcysteine ligase catalytic subunit (GCLC), at aspartate residue 499. Intriguingly, these truncated GCLC fragments compete with full-length GCLC in forming a heterocomplex with the modifier subunit (GCLM) but exhibit markedly reduced enzymatic activity. Crucially, using an aspartate-to-glutamate mutation knock-in (D499E-KI) mouse model that blocks GCLC truncation, we observed a notable delay in ARC formation compared to WT mice: Nearly 50% of D499E-KI mice remained cataract-free versus ~20% of the WT mice at their age of 20 months. Our findings concerning age-related GCLC truncation might be the key to understanding the profound reduction in lens GSH with age. By halting GCLC truncation, we can rejuvenate lens GSH levels and considerably postpone cataract onset.
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