The Impact of Donor Diabetes on Corneal Immune Cells and Corneal Transplant Survival

Abstract

Purpose : There is increasing evidence that the diabetic status of tissue donors can adversely impact corneal graft survival. Here, we evaluated the hypothesis that the diabetic state induces an altered corneal microenvironment with increased antigen-presenting cell (APC) maturation that in turn leads to heightened host sensitization and increased graft rejection.

Methods : Type I diabetes mellitus was induced in C57BL/6 mice by injecting 50mg/kg streptozocin (STZ) for 5 days. The altered glycemic state was confirmed by a glucometer. On day 28, mice with blood glucose levels of 300mg/dL were considered diabetic. Corneas were then harvested and either digested for analysis through flow cytometry, or grafted into normal BALB/c recipient mice. Two weeks after transplantation, immune cells from the corneas and draining lymph nodes (DLN) of recipient mice were analyzed by flow cytometry and allospecific cytokine production was evaluated through a mixed lymphocyte reaction.

Results : A significantly higher frequency of CD45⁺ cells (p=0.0009) and higher expression levels of MHC-II by APC (p=0.048) were observed in corneas from diabetic donors compared to normal mice. Allograft survival was decreased in diabetic donors (0%) compared to normal donors (52%, p=0.0002) through eight weeks of follow-up. The frequency of CD45⁺CD11b⁺ APC (p=0.014) as well as their expression of the maturation markers MHC-II (p=0.006), CD80 (p=0.007) and CD86 (p=0.03) was significantly increased in recipients receiving grafts from diabetics as compared to non-diabetic donors.

Conclusions : Our preliminary data suggest that diabetes mellitus leads to increased maturation of resident corneal immune cells and that transplantation of diabetic donor corneas leads to heightened host alloimmunity and increased graft rejection.

This is a 2021 ARVO Annual Meeting abstract.