ArticleInvestigative ophthalmology & visual science2016
Evidence of Dual Mechanisms of Glutathione Uptake in the Rodent Lens: A Novel Role for Vitreous Humor in Lens Glutathione Homeostasis.
Article in Investigative ophthalmology & visual science, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
What it found
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Who cites it
21 citing papers in PubMed, 35 citations in OpenAlex.
- Lens aging and disease: Molecular mechanisms, functional consequences, and pharmacological implications.Progress in retinal and eye research · 2026Review
- Transcriptomic Analysis of Human Lens Epithelium Tissue With and Without Cataract Surgery: Uncovering Novel Pathways of Post-Surgical Lens Epithelium Remodeling.Investigative ophthalmology & visual science · 2025Article
- In Vivo Assessment of an Antioxidant Hydrogel Vitreous Substitute.Journal of biomedical materials research. Part A · 2025Article
- Mefunidone Inhibits Inflammation, Oxidative Stress, and Epithelial-Mesenchymal Transition in Lens Epithelial Cells.Investigative ophthalmology & visual science · 2024Article
- Oxidative Stress, Glutaredoxins, and Their Therapeutic Potential in Posterior Capsular Opacification.Antioxidants (Basel, Switzerland) · 2024Review
- Minimizing Oxidative Stress in the Lens: Alternative Measures for Elevating Glutathione in the Lens to Protect against Cataract.Antioxidants (Basel, Switzerland) · 2024Review
- Prevention of age-related truncation of γ-glutamylcysteine ligase catalytic subunit (GCLC) delays cataract formation.Science advances · 2024Article
- Breaking Barriers: Nanomedicine-Based Drug Delivery for Cataract Treatment.International journal of nanomedicine · 2024Review
- Redox Regulation in Age-Related Cataracts: Roles for Glutathione, Vitamin C, and the NRF2 Signaling Pathway.Nutrients · 2023Review
- Protein kinase A activation alleviates cataract formation via increased gap junction intercellular communication.iScience · 2023Article
- Glutathione and Glutaredoxin in Redox Regulation and Cell Signaling of the Lens.Antioxidants (Basel, Switzerland) · 2022Review
- Impaired GSH biosynthesis disrupts eye development, lens morphogenesis and PAX6 function.The ocular surface · 2021Article
- Redox chemistry of lens crystallins: A system of cysteines.Experimental eye research · 2021Review
- Moderate oxidative stress promotes epithelial-mesenchymal transition in the lens epithelial cells via the TGF-β/Smad and Wnt/β-catenin pathways.Molecular and cellular biochemistry · 2021Article
- Mechanosensitive collaboration between integrins and connexins allows nutrient and antioxidant transport into the lens.The Journal of cell biology · 2020Article
- Characterisation of Glutathione Export from Human Donor Lenses.Translational vision science & technology · 2020Article
- Protein Stability and Photostability under In Vitro Vitreal Conditions - Implications for Long Acting Delivery of Protein Therapeutics for Ocular Disease.Pharmaceutical research · 2020Article
- Proteomic analysis of the glutathione-deficient LEGSKO mouse lens reveals activation of EMT signaling, loss of lens specific markers, and changes in stress response proteins.Free radical biology & medicine · 2017Article
- Reduced Glutathione Level Promotes Epithelial-Mesenchymal Transition in Lens Epithelial Cells via a Wnt/β-Catenin-Mediated Pathway: Relevance for Cataract Therapy.The American journal of pathology · 2017Article
- Transcriptome of the GSH-Depleted Lens Reveals Changes in Detoxification and EMT Signaling Genes, Transport Systems, and Lipid Homeostasis.Investigative ophthalmology & visual science · 2017Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
purposeLens glutathione synthesis knockout (LEGSKO) mouse lenses lack de novo glutathione (GSH) synthesis but still maintain >1 mM GSH. We sought to determine the source of this residual GSH and the mechanism by which it accumulates in the lens.
methodsLevels of GSH, glutathione disulfide (GSSG), and GSH-related compounds were measured in vitro and in vivo using isotope standards and liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis.
resultsWild-type (WT) lenses could accumulate GSH from γ-glutamylcysteine and glycine or from intact GSH, but LEGSKO lenses could only accumulate GSH from intact GSH, indicating that LEGSKO lens GSH content is not due to synthesis by a salvage pathway. Uptake of GSH in cultured lenses occurred at the same rate for LEGSKO and WT lenses, could not be inhibited, and occurred primarily through cortical fiber cells. In contrast, uptake of GSH from aqueous humor could be competitively inhibited and showed an enhanced Km in LEGSKO lenses. Mouse vitreous had >1 mM GSH, whereas aqueous had <20 μM GSH. Testing physiologically relevant GSH concentrations for uptake in vivo, we found that both LEGSKO and WT lenses could obtain GSH from the vitreous but not from the aqueous. Vitreous rapidly accumulated GSH from the circulation, and depletion of circulating GSH reduced vitreous but not aqueous GSH.
conclusionsThe above data provide, for the first time, evidence for the existence of dual mechanisms of GSH uptake into the lens, one mechanism being a passive, high-flux transport through the vitreous exposed side of the lens versus an active, carrier-mediated uptake mechanism at the anterior of the lens.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.