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Diego G Ogando, Shimin Li, Joseph A Bonanno; Corneal Lactate and Ammonia Concentrations Altered in Slc4a11 Knockouts. Invest. Ophthalmol. Vis. Sci. 2014;55(13):2029.
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SLC4A11 is a basolateral membrane transporter with permeability to H+ and ammonia. Mutations in SLC4A11 cause corneal dystrophies. Slc4a11 KO mice show corneal edema at birth and a decrease in the endothelial cell density as they age. Current endothelial pump hypothesis states that key membrane transporters work to facilitate lactate efflux. Therefore, we predict that stromal lactate will be increased in endothelial dystrophic models. Additionally we test the hypothesis that corneal NH3 concentration is altered in Slc4a11 KO mice as this protein has NH3 permeability.
Corneal thickness was evaluated by Spectral-Domain Optical Coherence Tomography in vivo. Lactate and NH3 were measured in corneal extracts by a fluorescent enzyme assay and ion specific electrodes respectively. All studies were performed at 12 weeks of age.
Corneal thickness was significantly higher in Slc4a11 KO mice (KO: 181±25 µm, n=14 vs WT: 95±9, n=13; p=1.06 x 10-9). Consistent with compromised pump function in Slc4a11 corneal endothelium, corneal lactate concentration was significantly higher in the KO (KO: 0.247±0.038 nmol lactate/mg dry weight, n=10 vs WT: 0.096±0.023, n=13; p=0.01). Corneal NH3 concentration was significantly lower in Slc4a11 corneas (KO: 1.508±0.202 nmol NH3/mg dry weight, n=8 vs WT: 6.390±2.400, n=6; p=0.024), which may indicate a deficient transport of NH3 in the apical to basolateral direction.
(1) The increased concentration of lactate in this corneal dystrophy model is consistent with the role of lactate efflux in the corneal endothelial pump. (2) The altered corneal NH3 concentration is consistent with SLC4A11 NH3 permeability, however the significance of ammonia transport in the cornea is unknown.
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