The corresponding author Philip Maier had full usage of all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis

The corresponding author Philip Maier had full usage of all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Notes The authors declare no conflict of interest.. the slit lamp. Statistics For statistical analysis, all computations were performed using the R-Software system.17 We performed a Cox proportional hazards model including three co-variates: storage time, patient’s age at time of surgery, and the risk status of the patient. Furthermore, we performed KaplanCMeier survival estimations of event-free survival times. results of the kinetics regarding the stromal APC decrease with the fastest depletion of stromal APCs during Hydroxocobalamin (Vitamin B12a) the first 7 days of organ Hydroxocobalamin (Vitamin B12a) culture13 and our observation that the highest rate of rejections was in the group of grafts with storage times below 14 days compared with longer storage periods (observe Figure 3) it might be concluded that stromal and not only epithelial DCs have an important role in corneal allograft rejection. Simon em et al /em 14 reported in their retrospective clinical study that a storage time of 7 days or more has been observed to be associated with a beneficial effect on allograft survival. They also found that the rate of allograft rejection was significantly lower for patients receiving donor corneas after prolonged storage ( 7 days). However, this was only statistically significant for high-risk (not for normal risk) patients. In their study, the number of graft rejections in the low-risk group, which comprised only 135 patients was probably underpowered, resulting in a nonsignificant effect. However, it is not clear whether the reduction of APCs is the correct explanation for the graft-protecting effect of prolonged organ culture. Nevertheless, direct and indirect allosensitization seem to have an important role in corneal allograft rejection.4, 5, 6, 22 Even small numbers of these cells found in the mouse cornea were able to induce corneal allosensitization.23 Furthermore, it has been shown that donor-derived corneal APCs can be found in the draining lymph node and the spleen of the recipient within only a few hours following corneal transplantation.6 Rejection episodes following renal transplantations, for example, were reduced after inactivation of donor-derived hematopoietic cells, leading to an increased allograft survival time.24 Reduction of APCs in the cornea may be easily achieved by prolonged organ culture as compared with renal grafts, KMT6A where the kidneys need to be perfused with anti-CD45 antibodies. Besides the quantity of APCs, the endothelial cell density also decreases over time during organ culture. This difference in endothelial cell density can be found in the recipients for at least 1 year following penetrating keratoplasty.25 Therefore, a shorter storage time might be correlated with longer clear graft survival if the patient does not experience an endothelial immune reaction. Therefore, in normal risk situations, shorter storage times should be preferred. Besides the decrease of APCs and the decrease of endothelial cells in the graft during organ culture, various other factors, like the clinical risk profile of the patients, HLA-matching, postoperative immunosuppression, or the compliance of the patients, need to be considered regarding the individual rejection risk and obvious graft survival. Therefore, the optimum storage time with respect to the patient’s overall graft prognosis needs to be defined by the eye bank and the doctor. Acknowledgments All authors met the following criteria regarding their contribution to this work: (1) substantial contributions to conception and design, or acquisition of data, or analysis and interpretation of data; (2) drafting the article or revising it critically for important Hydroxocobalamin (Vitamin B12a) intellectual content; (3) final approval of the version to be published. The corresponding author Philip Maier experienced full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Notes The authors declare no discord of interest..