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2025 OMIG Abstract
POSTER PRESENTATION
Post-Transplant Cyclophosphamide Modulates Immune Responses and Prolongs Graft Survival in a Murine Model of High-Risk Corneal Transplantation
Ali Khodor, Yasufumi Tomioka, Leonardo De Castro, Carolina Moreira, Rosa Alvarado Villacorta, Gabriella Mezzich, Dietlinde Wolf, Robert B. Levy, Victor L. Perez
Bascom Palmer Eye Institute, University of Miami, Miami, Florida
Purpose: To evaluate outcomes of a novel post-transplant cyclophosphamide (Cy) regimen in a murine model of high-risk corneal transplant (HR-CT).
Methods: Fully MHC-mismatched corneal transplants (C57BL/6 to BALB/c) were performed. Mice were randomized into G1=no treatment (n=11), G2=high-dose Cy (70 mg/kg x2, week 1, n=5), G3=high + low-dose Cy (70 mg/kg x2, week 1; 25 mg/kg x2, weeks 2–3, n=4). Corneal clarity, assessed weekly by masked observers using a standardized grading scale, was the primary endpoint. Mice were monitored for 8 weeks. Flow cytometry at endpoint assessed Th1/Th17 cells in ocular tissues and lymphoid organs.
Results: Twenty mice were included. Median graft survival was 21 days (18% survival, G1, n=11), 35 days (20% survival, G2, n=5), and 50 days (50% survival, G3, n=4). G3 recipients exhibited prolonged graft clarity and delayed rejection: hazard ratio of G1 vs G3 was 3.7 (95% CI, 0.94 to 14.4) at week 4, and 2.1 (95% CI, 0.6 to 7.5) at week 8. Flow cytometry revealed decreased Th1 and Th17 proportions in G3 compared to G1. In the cornea, Th1: 32% (G1/2) vs 19% (G3); Th17: 11% (G1/2) vs 2.6% (G3). In the lacrimal gland, Th1 decreased from 30% (G1) to 22% (G3); Th17: 3.7% (G1/2) vs 2.2% (G3). In draining lymph nodes, G3 showed decreased Th1 compared to G1 (3.3% vs 5%, p<.05) while retaining total T cell count.
Conclusions: Cyclophosphamide improved corneal allo-graft survival and modulated ocular surface immunity, evidenced by reducing Th1/Th17 responses. These findings support the development of cyclophosphamide based therapeutic strategies to prevent rejection of HR-CT.
Disclosure: N (AK, YT, LD, CM, RAV, GM, DW)
C (RBL, Eniale Immunotherapeutics, Inc; VLP, Alumis, BrightStar, Brill Engine, Dompe, Kala, Oculis, Regeneron, Santen, Sylentis, Thea, BRIM, EmmeCell, Grifols, Ocubio, Trefoil (Equity and Advisory Board)
Support:
NIH/NEI R01EY030283 (RBL, VLP)
NIH/NEI R01EY024484 (RBL, VLP)
Research to Prevent Blindness- Unrestricted Grant (GR004596-1) (VLP)
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