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T. Funaki, S. K. Chauhan, M. H. Dastjerdi, U. Jurkunas, R. Dana; Impact of Alloimmunity on Corneal Endothelium in Transplantation. Invest. Ophthalmol. Vis. Sci. 2009;50(13):1963.
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© ARVO (1962-2015); The Authors (2016-present)
Corneal endothelial cells (CEC) are the principal target of alloimmunity in corneal transplantation. CEC are non-dividing cells, and corneal transparency is dependent on a sufficient number of functional endothelial cells. The purpose of the present study is to investigate the impact of alloimmunity on viability and integrity of endothelial cells after corneal transplantation.
BALB/c and C57BL/6 mice were used as recipients and donors for orthotopic corneal transplantation. Naïve C57BL/6 corneal cups were co-cultured with total CD3+ or CD4+ T cells isolated from the draining LN of syngeneic recipients, allograft acceptors and allograft rejectors, and then stained with ZO-1 and TUNEL to visualize the CEC and apoptosis, respectively. Grafted corneas from different transplant groups were harvested and stained with ZO-1 to analyze CEC’s density, polymegathism and pleomorphism using Confoscan4 software (NIDEK CO., LTD, U.S.A).
T cells isolated from allograft rejectors induced higher apoptosis of CEC compared to those isolated from allograft acceptors in corneal cup assays. Compared to total CD3+ T cells, CD4+ T cells had more potential to induce CEC apoptosis. However, T cells isolated from syngeneic recipients were unable to induce significant apoptosis of CEC. In transplanted corneas, a significant loss of CEC was observed primarily in the graft-area in all types of graft recipients. However, the loss of CEC over time was more progressive in allograft recipients compared to syngeneic recipients. CEC density in rejected-grafts was significantly lower than those in accepted-grafts. CEC were undetectable in rejected-grafts at week 8 post-transplantation. Significantly higher frequencies of CEC with altered morphology including polymegathism and pleomorphism were observed in rejected-grafts compared to those in accepted- and syngeneic-grafts.
Our findings confirm the crucial role of allogeneic CD4+ T cells in inducing apoptosis of CEC in corneal transplantation. In addition, our data elucidate that the loss of CEC in allografts is followed by a significant alteration in the integrity and morphology of endothelial cells which may affect their functionality.
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