Function-Related Protein Expression in Fuchs Endothelial Corneal Dystrophy Cells and Tissue Models

Fuchs endothelial corneal dystrophy (FECD) is a corneal pathology that affects the endothelial cell’s ability to maintain deturgescence, resulting in a progressive loss of corneal transparency. In this study, we investigated the expression of function-related proteins in corneal endothelial cells using FECD or healthy corneal endothelial cells, either in a cell culture two-dimensional model or in an engineered corneal endothelium three-dimensional tissue model. No statistically significant difference in gene regulation was observed for the function-related families ATP1, SLC4, SLC16, AQP, TJP, and CDH between the FECD and the healthy cell models. Similarly, no difference in barrier integrity (transendothelial electrical resistance measurements and permeability assays) was observed in vitro between FECD and healthy cultured cells. Protein expression of the key function-related families was decreased for Na+/K+-ATPase α1 subunit, monocarboxylate transporters 1 and 4 in native ex vivo end-stage FECD specimens, whereas it returned to levels comparable to that of healthy tissues in the engineered FECD model. These results indicate that cell expansion and tissue engineering culture conditions can generate a corneal endothelium from pathologic FECD cells, with levels of function-related proteins similar to that of healthy tissues. Overall, these results explain why it is possible to reform a functional endothelium using corneal endothelial cells isolated from nonfunctional FECD pathologic specimens. Fuchs endothelial corneal dystrophy (FECD) is a corneal pathology that affects the endothelial cell’s ability to maintain deturgescence, resulting in a progressive loss of corneal transparency. In this study, we investigated the expression of function-related proteins in corneal endothelial cells using FECD or healthy corneal endothelial cells, either in a cell culture two-dimensional model or in an engineered corneal endothelium three-dimensional tissue model. No statistically significant difference in gene regulation was observed for the function-related families ATP1, SLC4, SLC16, AQP, TJP, and CDH between the FECD and the healthy cell models. Similarly, no difference in barrier integrity (transendothelial electrical resistance measurements and permeability assays) was observed in vitro between FECD and healthy cultured cells. Protein expression of the key function-related families was decreased for Na+/K+-ATPase α1 subunit, monocarboxylate transporters 1 and 4 in native ex vivo end-stage FECD specimens, whereas it returned to levels comparable to that of healthy tissues in the engineered FECD model. These results indicate that cell expansion and tissue engineering culture conditions can generate a corneal endothelium from pathologic FECD cells, with levels of function-related proteins similar to that of healthy tissues. Overall, these results explain why it is possible to reform a functional endothelium using corneal endothelial cells isolated from nonfunctional FECD pathologic specimens. The corneal endothelium forms a monolayer of cells on the posterior surface of the cornea. It is responsible for corneal deturgescence, keeping the stroma partially dehydrated, which is a prerequisite for corneal transparency.1Edelhauser H.F. The balance between corneal transparency and edema: the Proctor Lecture.Invest Ophthalmol Vis Sci. 2006; 47: 1754-1767Crossref PubMed Scopus (168) Google Scholar The barrier and pump functions of the endothelium are responsible for maintaining corneal transparency by regulating stromal hydration. 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S. in vivo model for Fuchs endothelial corneal dystrophy.Invest Ophthalmol Vis Sci. 2012; PubMed Scopus Google Scholar the gene results of and by No statistically significant difference was observed in the gene and the between FECD and healthy 1, and Protein expression by a of Na+/K+-ATPase α1 in native FECD with healthy an endothelium on a using FECD cells expression to a similar to that of an endothelium engineered using healthy cells No difference was observed in the protein expression of Na+/K+-ATPase between FECD and healthy native and no expression was observed in the engineered healthy and The of the family are anion exchangers 1 to endothelial cells expressed and the of the endothelial cells expressed membrane of and No in expression observed between FECD and healthy cells for proteins The borate cotransporter and FECD SLC4A11 to have a expression in FECD this difference was statistically significant of the of expression in the It has been that the sodium bicarbonate protein was decreased in a model of S. J.D. S. in vivo model for Fuchs endothelial corneal dystrophy.Invest Ophthalmol Vis Sci. 2012; PubMed Scopus Google Scholar to the absence of difference in gene expression of between cultured healthy and FECD cells by The sodium bicarbonate protein was in native and engineered tissues of healthy and FECD cells The gene family has of which and monocarboxylate MCT4, MCT2, and The gene role and regulation in and Med. PubMed Scopus Google Scholar an expression of and the to of these expression No difference of expression between FECD and healthy cells was observed using gene and genes to in J.A. of ion transporters and protein in Fuchs' 2014; Google Scholar was for these genes no difference in expression between the FECD and the healthy cells. protein an absence of expression for and in native FECD specimens, whereas in the healthy specimens. The engineered endothelium using healthy and FECD cells the protein was in the endothelium engineered using healthy and FECD cells 4 the results of the aquaporin protein and a expression of of of of and of expressed in a and Protein of aquaporin 1 by a of which gene expression results FECD cells no significant in gene and protein expression of was the most expressed in as was occludens protein for the zonula occludens protein 1 family gene expression in FECD and healthy cultured cells No significant difference in was between FECD Ω cm2) and healthy Ω The Ω cm2) a in to cell within the of culture No difference in permeability was observed between FECD to and healthy or between FECD and FECD is a disease that and results in a endothelial The of the endothelium a Jr., Descemet's with endothelial in a corneal 2005; PubMed Google Scholar or models. for the of in ability to For example, the role of the endothelial cells in the of the disease is The ability to and an FECD endothelium on a a to between cell and pathologic such among others, S. 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PubMed Scopus Google Scholar In this we a cell model and a tissue model to the expression of function-related proteins and the endothelial barrier integrity of cultured FECD endothelial cells. cell no difference in the expression of ATP1, SLC4, SLC16, AQP, and families and in the endothelial barrier integrity between FECD and healthy cell was cells similar to healthy cells, of from this loss of the FECD phenotype on by of the cells absence of a pathologic The mechanism by the that FECD in the the The FECD in the cells at of the with and cells in the of the Cell the of these cells with endothelial The mechanism the absence in culture of a pathologic such an basement membrane or cells to to is that in vitro the culture that to that are in the in vivo In a of these mechanisms to pharmacologic either by of the cells, by of the cell or by that are in These of the disease and the for corneal These results are in with that an engineered FECD endothelium can maintain corneal and transparency in a in vivo S. J.D. S. in vivo model for Fuchs endothelial corneal dystrophy.Invest Ophthalmol Vis Sci. 2012; PubMed Scopus Google Scholar this study an of which to that the cultured FECD cells the is by the of a of the cells of engineered FECD B. M. S.P. S. and expression in Fuchs endothelial corneal dystrophy cells and tissue A. PubMed Scopus Google Scholar that is from the of the It that the of Na+/K+-ATPase pump pump in human corneal Ophthalmol Vis Sci. Google Scholar, of functional and human corneal Eye Res. PubMed Scopus Google Scholar, of in human corneal Eye Res. PubMed Scopus Google Scholar, Fuchs' endothelial dystrophy pump Ophthalmol Vis Sci. Google Scholar and the of the barrier J.D. Fuchs' endothelial dystrophy: a at an PubMed Scopus Google Scholar observed in FECD to the results the protein and of Na+/K+-ATPase MCT1, and in native J.A. of ion transporters and protein in Fuchs' 2014; Google Scholar, pump in human corneal Ophthalmol Vis Sci. Google Scholar, of functional and human corneal Eye Res. PubMed Scopus Google Scholar, of in human corneal Eye Res. PubMed Scopus Google Scholar, Fuchs' endothelial dystrophy pump Ophthalmol Vis Sci. Google Scholar that in expression of sodium bicarbonate was associated with J.A. of ion transporters and protein in Fuchs' 2014; Google Scholar expression levels of Na+/K+-ATPase and between the native and the engineered the protein expression was by the and the healthy engineered we it was to FECD and by the of the aquaporin family in gene expression between with proteins in this to why cells of aquaporin is the of this are expressed in the corneal endothelium, these explain why to cause corneal edema in the J.R. A.S. in corneal water permeability and of transparency PubMed Scopus Google Scholar S.R. N. B. Altered expression of in and Fuchs' dystrophy 2004; PubMed Google Scholar in the in vitro with this study the of FECD corneal endothelium to ability to that of the FECD endothelium is to which to investigated in and of the and and for in Fuchs endothelial corneal dystrophy and the and for and for the with

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