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Inducible Slc4a11 Knockout Triggers Corneal Edema Through Perturbation of Corneal Endothelial Pump
Journal article   Open access   Peer reviewed

Inducible Slc4a11 Knockout Triggers Corneal Edema Through Perturbation of Corneal Endothelial Pump

Diego G Ogando, Rajalekshmy Shyam, Edward T Kim, Yen-Chiao Wang, Chia-Yang Liu and Joseph A Bonanno
Investigative ophthalmology & visual science, Vol.62(7), p.28
06/01/2021
DOI: 10.1167/iovs.62.7.28
PMCID: PMC8826551
PMID: 34190974
url
https://doi.org/10.1167/iovs.62.7.28View
Published (Version of record) Open Access

Abstract

The conventional Slc4a11 knockout (KO) shows significant corneal edema at eye opening, a fact that complicates the study of the initial events leading to edema. An inducible KO would provide opportunities to examine early events following loss of Slc4a11 activity. Slc4a11 Flox (SF) mice were crossed with mice expressing the estrogen receptor Cre Recombinase fusion protein and fed tamoxifen (Tm) for two weeks. Corneal thickness (CT) was measured by OCT. At eight weeks endpoint, oxidative damage, tight junction integrity, stromal lactate concentration, endothelial permeability, differentially expressed transporters, and junction proteins were determined. Separately, a keratocyte only inducible Slc4a11 KO was also examined. At four weeks post-Tm induction Slc4a11 transcript levels were 2% of control. Corneal thickness increased gradually and was 50% greater than Wild Type (WT) after eight weeks with significantly altered endothelial morphology, increased nitrotyrosine staining, significantly higher stromal lactate, decreased expression of lactate transporters and Na-K ATPase activity, higher ATP, altered expression of tight and adherens junctions, and increased fluorescein permeability. No significant differences in CT were found between WT and keratocyte only Slc4a11 KO. The Slc4a11 inducible KO shows development of a similar phenotype as the conventional KO, thereby validating the model and providing a tool for further use in examining the sequence of cellular events by use of noninvasive in vivo physiological probes.
 Animals Anion Transport Proteins - genetics Anion Transport Proteins - metabolism Corneal Edema - genetics Corneal Edema - metabolism Corneal Edema - physiopathology Disease Models, Animal Endothelium, Corneal - physiology Mice Mice, Knockout - genetics Mice, Knockout - metabolism Oxidative Stress Symporters - genetics

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