The Biologic Character of Donor Corneal Endothelial Cells Influences Endothelial Cell Density Post Successful Corneal Transplantation
Koji Kitazawa, Munetoyo Toda, Morio Ueno, Asako Uehara, Chie Sotozono, Shigeru Kinoshita
Abstract
PurposeCorneal endothelial cell density (ECD) gradually decreases after corneal transplantation by unknown biological, biophysical or immunological mechanism. To assess the association between donor corneal endothelial cell (CEC) maturity in culture and postoperative endothelial cell loss (ECL) after successful corneal transplantation.DesignProspective cohort study.ParticipantsThis cohort study was conducted at Baptist Eye Institute, Kyoto, Japan, between October 2014 and October 2016. It included 68 patients with a 36-month follow-up period who had undergone successful Descemet’s stripping automated endothelial keratoplasty (DSAEK) or penetrating keratoplasty (PK).MethodsHuman CECs (HCECs) from remaining peripheral donor corneas were cultured and evaluated for maturity by surface markers (CD166+, CD44-/dull, CD24-, and CD105-) using fluorescence activated cell sorting (FACS). Postoperative ECD was assessed according to the mature-differentiated HCEC contents: high maturity group: >70%, middle maturity group: 10–70%, low maturity group: <10%. The successful rate of ECD maintained at 1,500 cells/mm2 at 36-months postoperative was analyzed using the log-rank test.Main Outcome MeasuresECD and ECL at 36-months postoperative.ResultsThe 68 included patients (Mean [SD] age 68.1 [13.6] years, 47.1% female, 52.9% DSAEK). The high, middle, and low maturity groups included 17, 32, and 19 eyes. At 36-months postoperative, the mean (SD) ECD significantly decreased to 911 (388) cells/mm2 by 66% in the low maturity group, compared to 1,604 (436) by 40% and 1,424 (613) cells/mm2 by 50% in the high and middle maturity groups (P < 0.001 and P = 0.007, respectively) and the low maturity group significantly failed to maintain ECD at 1,500 cells/mm2 at 36-months postoperative (P < 0.001). Additional ECD analysis for DSAEK patients alone displayed a significant failure to maintain ECD at 1,500 cells/mm2 at 36-months postoperative (P < 0.001).ConclusionsThe high content of mature-differentiated HCECs expressed in culture by the donor peripheral cornea was coincident well with low endothelial cell loss, suggesting that a high maturity CEC content predicts long-term graft survival. Understanding the molecular mechanism for maintaining HCEC maturity could elucidate the mechanism of ECL after corneal transplantation and aid in developing effective interventions.