ArticleInvestigative ophthalmology & visual science2012
Lactate-H⁺ transport is a significant component of the in vivo corneal endothelial pump.
Article in Investigative ophthalmology & visual science, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 33 citations in OpenAlex.
- Mutations in the TMCO3 Gene are Associated with Cornea Guttata and Anterior Polar Cataract.Scientific reports · 2016Trial
- Metabolic and redox adaptations of the corneal endothelium: From metabolic plasticity to therapeutic opportunities.Redox biology · 2026Review
- Review
- Investigating the Role of TGF-β Signaling Pathways in Human Corneal Endothelial Cell Primary Culture.Cells · 2023Article
- Intracellular pH affects mitochondrial homeostasis in cultured human corneal endothelial cells prepared for cell injection therapy.Scientific reports · 2022Article
- Rescue of the Congenital Hereditary Endothelial Dystrophy Mouse Model by Adeno-Associated Viruse-MediatedOphthalmology science · 2022Article
- Monocarboxylate Transporters: Role and Regulation in Corneal Diabetes.Analytical cellular pathology (Amsterdam) · 2022Article
- Inducible Slc4a11 Knockout Triggers Corneal Edema Through Perturbation of Corneal Endothelial Pump.Investigative ophthalmology & visual science · 2021Article
- Bicarbonate activates glycolysis and lactate production in corneal endothelial cells by increased pHExperimental eye research · 2020Article
- Polarized Expression of Ion Channels and Solute Carrier Family Transporters on Heterogeneous Cultured Human Corneal Endothelial Cells.Investigative ophthalmology & visual science · 2020Article
- Corneal Endothelial Pump Coupling to Lactic Acid Efflux in the Rabbit and Mouse.Investigative ophthalmology & visual science · 2020Article
- ZEB1 insufficiency causes corneal endothelial cell state transition and altered cellular processing.PloS one · 2019Article
- Proton Transport Chains in Glucose Metabolism: Mind the Proton.Frontiers in neuroscience · 2018Review
- Conditionally Immortal Slc4a11-/- Mouse Corneal Endothelial Cell Line Recapitulates Disrupted Glutaminolysis Seen in Slc4a11-/- Mouse Model.Investigative ophthalmology & visual science · 2017Article
- Fluid transport by the cornea endothelium is dependent on buffering lactic acid efflux.American journal of physiology. Cell physiology · 2016Article
- Quercetin attenuates lactate production and extracellular matrix secretion in keratoconus.Scientific reports · 2015Article
- Tear metabolite changes in keratoconus.Experimental eye research · 2015Article
- Efficient Generation of Human Embryonic Stem Cell-Derived Corneal Endothelial Cells by Directed Differentiation.PloS one · 2015Article
- CD147 required for corneal endothelial lactate transport.Investigative ophthalmology & visual science · 2014Article
- In vitro model suggests oxidative stress involved in keratoconus disease.Scientific reports · 2014Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
purposeTo confirm the expression of monocarboxylate transporters (MCT) 1, 2, and 4 in rabbit CE and to test the hypothesis that cellular buffering contributed by HCO₃⁻, NBCe1, and carbonic anhydrase (CA) activity facilitates lactate-H⁺ efflux thereby controlling corneal hydration in vivo.
methodsMCT1-4 expression of rabbit endothelium was examined by Western blotting and immunofluorescence staining. Lactate-induced acidification (LIA) was measured in perfused CE in the presence and absence of HCO₃⁻ and acetazolamide (ACTZ) using tissue treated with siRNA specific to MCT1, 2, and 4. Corneal thickness and lactate concentration were measured in New Zealand White rabbits treated with the topical CA inhibitor Azopt, and from eyes that were injected intracamerally with ouabain, disodium 4,4'-diisothiocyanatostilbene-2,2'-disulfonate (DIDS), and shRNA specific to the 1Na⁺:2HCO₃⁻ cotransporter NBCe1.
resultsMCT1 and MCT4 are localized to the lateral membrane, while MCT2 is apical. Cell pH measurements showed LIA in response to 40 mM lactate in bicarbonate free (BF) Ringer's that was inhibited by niflumic acid and by MCT siRNA knockdown, and significantly reduced in the presence of HCO₃⁻. Lactate-dependent proton flux in vitro was not significantly greater in the presence of HCO₃⁻ or reduced by ACTZ. However, when active transport, NBCe1, or CA activity was disrupted in vivo, corneal edema ensued and was associated with significant corneal lactate accumulation.
conclusionsMCT1, 2, and 4 are expressed in rabbit CE on both the apical and basolateral surfaces and function to transport lactate-H⁺. Lactate-H⁺ flux is facilitated by active transport, HCO₃⁻ transport and CA activity, disruption of which causes corneal edema in vivo and indicates that facilitation of lactate efflux is a component of the endothelial pump.
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