ArticleInvestigative ophthalmology & visual science2017
The Eye Drop Preservative Benzalkonium Chloride Potently Induces Mitochondrial Dysfunction and Preferentially Affects LHON Mutant Cells.
Article in Investigative ophthalmology & visual science, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
44 citing papers in PubMed, 1 synthesis or guideline pooled it, 122 citations in OpenAlex.
- The Role of Mitochondrial DNA Variation in Drug Response: A Systematic Review.Frontiers in genetics · 2021Pooled it
- Benzalkonium Chloride-Induced Nephrotoxicity in 2D Cultures and a Human Kidney-on-a-Chip System.Environmental science & technology · 2026Article
- Differential and Sex-Specific Toxicity of Aspirated Quaternary Ammonium Compounds.Environmental science & technology · 2026Article
- Current and Developing Therapeutics for Dry Eye Disease: Targeting Ion Channels.Current issues in molecular biology · 2026Review
- Effects of Benzalkonium Chloride, a Preservative in Topical Drugs, on the Barrier Function of Human Corneal Epithelial Cells.Translational vision science & technology · 2025Article
- Can the choice of artificial tears harm patients? A narrative review with an overview of the Nordic market.Acta ophthalmologica · 2025Review
- In Vitro Toxicity of Cetalkonium Chloride on Corneal Epithelial Cells.Pharmaceutics · 2025Article
- Assessment of the toxic effect of benzalkonium chloride on human limbal stem cells.Scientific reports · 2025Article
- Topical Ocular Drug Delivery: The Impact of Permeation Enhancers.Pharmaceutics · 2025Review
- The new bilastine eye drop formulation protects against conjunctival dehydration and promotes corneal wound healing in a comparative in vitro study.Scientific reports · 2025Article
- Multifaceted mitochondrial as a novel therapeutic target in dry eye: insights and interventions.Cell death discovery · 2024Review
- SPARC overexpression in allogeneic adipose-derived mesenchymal stem cells in dog dry eye model induced by benzalkonium chloride.Stem cell research & therapy · 2024Article
- Benzalkonium chloride greatly deteriorates the biological activities of human corneal stroma fibroblasts in a concentration-dependent manner.Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie · 2024Article
- Development and Application of a Multidimensional Database for the Detection of Quaternary Ammonium Compounds and Their Phase I Hepatic Metabolites in Humans.Environmental science & technology · 2024Article
- Antimicrobial cetylpyridinium chloride causes functional inhibition of mitochondria as potently as canonical mitotoxicants, nanostructural disruption of mitochondria, and mitochondrial CaFood and chemical toxicology : an international journal published for the British Industrial Biological Research Association · 2024Article
- The Optic Nerve at Stake: Update on Environmental Factors Modulating Expression of Leber's Hereditary Optic Neuropathy.Biomedicines · 2024Review
- Aprepitant Restores Corneal Sensitivity and Reduces Pain in DED.Translational vision science & technology · 2024Article
- Genome-wide RNA sequencing of ocular fibroblasts from glaucomatous and normal eyes: Implications for glaucoma management.PloS one · 2024Article
- Short-term effects of ophthalmic topical 0.01% atropine on the ocular surface, pupil size, and subsequent subjective quality of vision in young myopic Chinese adults.Frontiers in medicine · 2024Article
- Quaternary Ammonium Compounds: A Chemical Class of Emerging Concern.Environmental science & technology · 2023Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
Purpose: Benzalkonium chloride (BAK) is the most commonly used eye drop preservative. Benzalkonium chloride has been associated with toxic effects such as "dry eye" and trabecular meshwork degeneration, but the underlying biochemical mechanism of ocular toxicity by BAK is unclear. In this study, we propose a mechanistic basis for BAK's adverse effects. Method: Mitochondrial O2 consumption rates of human corneal epithelial primary cells (HCEP), osteosarcoma cybrid cells carrying healthy (control) or Leber hereditary optic neuropathy (LHON) mutant mtDNA [11778(G>A)], were measured before and after acute treatment with BAK. Mitochondrial adenosine triphosphate (ATP) synthesis and cell viability were also measured in the BAK-treated control: LHON mutant and human-derived trabecular meshwork cells (HTM3). Results: Benzalkonium chloride inhibited mitochondrial ATP (IC50, 5.3 μM) and O2 consumption (IC50, 10.9 μM) in a concentration-dependent manner, by directly targeting mitochondrial complex I. At its pharmaceutical concentrations (107-667 μM), BAK inhibited mitochondrial function >90%. In addition, BAK elicited concentration-dependent cytotoxicity to cybrid cells (IC50, 22.8 μM) and induced apoptosis in HTM3 cells at similar concentrations. Furthermore, we show that BAK directly inhibits mitochondrial O2 consumption in HCEP cells (IC50, 3.8 μM) at 50-fold lower concentrations than used in eye drops, and that cells bearing mitochondrial blindness (LHON) mutations are further sensitized to BAK's mitotoxic effect. Conclusions: Benzalkonium chloride inhibits mitochondria of human corneal epithelial cells and cells bearing LHON mutations at pharmacologically relevant concentrations, and we suggest this is the basis of BAK's ocular toxicity. Prescribing BAK-containing eye drops should be avoided in patients with mitochondrial deficiency, including LHON patients, LHON carriers, and possibly primary open-angle glaucoma patients.
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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.