Analysis of sex-mismatched human corneal transplants by fluorescence in situ hybridization of the sex-chromosomes.

The fate of the cells of corneal transplants has been controversial from the early days of keratoplasty. Various methods such as histological evaluation, radiolabeling of donor cells or Barr-body analysis have been applied to clarify the issue. However, the question whether the transplanted cells are replaced or survive, remains unsolved. In this study, we applied fluorescence in situ hybridization (FISH) of the X- and Y-chromosomes in paraffin sections of explanted sex-mismatched corneal transplants to distinguish between host and donor cells. Fourteen sex-mismatched cases with various reasons for explantation and different postoperative time intervals ranging from 11 months to 30 years were analysed. We found that all cell types, including epithelium, keratocytes and endothelial donor cells were replaced in most cases as early as 1 year after transplantation. In three cases, however, up to 26% of donor keratocytes were still detected up to 4.5 years after transplantation, demonstrating a certain individual variability in the process of replacement. Further studies must show if the extent and timing of donor cell replacement in clinically successful, totally clear transplants is different. Our results are in keeping with the phenomenon of recurrences of corneal dystrophies in the graft, the significant postoperative decline of the endothelial cell density, the fact that typical graft rejections usually take place within 1-2 years postoperatively and that relatively late rejections can occur in rare cases probably due to some surviving stromal keratocytes. Donor cell replacement is a special feature of corneal transplants when compared with other kinds of organ transplants and might be due to the presence of the same tissue type in the immediate neighbourhood of the graft. Copyright 1999 Academic Press.