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Distribution of non-gal antigens in pig cornea: relevance to corneal xenotransplantation. Cornea 2014 Apr;33(4):390-7

Date

02/04/2014

Pubmed ID

24488129

DOI

10.1097/ICO.0000000000000069

Scopus ID

2-s2.0-84896395006   24 Citations

Abstract

PURPOSE: The aim of this study was to investigate the distribution of antigens other than galactose-I?-1,3-galactose (Gal) (non-Gal) recognized by human and rhesus monkey serum antibodies in the I?-1,3-galactosyltransferase gene-knockout (GTKO) pig cornea.

METHODS: The distribution of non-Gal, specifically N-glycolylneuraminic acid (NeuGc), in the corneas from wild-type (WT) and GTKO pigs was identified. Corneal sections from WT and GTKO pigs were incubated with human or rhesus monkey serum to determine immunoglobulin (Ig)M and IgG binding to corneal tissue by means of fluorescent microscopy.

RESULTS: Strong expression of NeuGc was found in all layers of both WT and GTKO pig corneas. In both humans and monkeys, antibody binding (IgG > IgM) to GTKO was found to be weaker than that to entire WT pig corneas, but in both, most antibody binding, especially IgG, was to the epithelium. There was weak diffuse antibody binding, especially of IgG, to the corneal stroma, suggesting binding to antigens expressed on collagen. There was no or minimal binding of IgM/IgG to the corneal endothelium.

CONCLUSIONS: Although the cornea is avascular, antibodies in primate serum can bind to pig antigens, especially on epithelial cells and stromal collagen. Although the binding to entire GTKO corneas was weaker than that to WT corneas, deletion of the expression of NeuGc and expression of human complement-regulatory proteins in the pig cornea will be important if prolonged clinical corneal xenograft survival is to be achieved.

Author List

Cohen D, Miyagawa Y, Mehra R, Lee W, Isse K, Long C, Ayares DL, Cooper DK, Hara H

Author

Whayoung Lee MD Assistant Professor in the Pathology department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Adult
Animals
Aorta, Thoracic
Autoantigens
Binding Sites, Antibody
Cornea
Corneal Transplantation
Disaccharides
Fluorescent Antibody Technique, Indirect
Galactosyltransferases
Gene Knockout Techniques
Humans
Immunoglobulin G
Immunoglobulin M
Macaca mulatta
Microscopy, Fluorescence
Middle Aged
Neuraminic Acids
Swine
Tissue Donors
Transplantation, Heterologous