Immune Responses in Rodent Whole Eye Transplantation: Elucidation and Preliminary Investigations Into Rejection Diagnosis and Monitoring

Authors

Bing Li
Yong Wang
Charles R Owens
Touka Banaee
Charleen T Chu
Kayvon Jabbari
Anna D Lee
Neil J Khatter
Alan G Palestine
An-Jey A Su
Christene A Huang
Kia M Washington

Language

English

Publication Date

1-1-2025

Journal

Frontiers in Immunology

DOI

10.3389/fimmu.2025.1475055

PMID

39944695

PMCID

PMC11814173

PubMedCentral® Posted Date

1-29-2025

PubMedCentral® Full Text Version

Post-print

Abstract

Background: Whole Eye Transplantation (WET) offers potential for vision restoration but is hindered by the complex challenge of immune rejection. Understanding and closely monitoring these immunological responses is crucial for advancing WET. This study delves into the timeline and nature of immune responses in a rodent model of WET without immunosuppression, aiming to elucidate a detailed picture of the immune landscape post-transplantation and establish innovative diagnostic and monitoring methods.

Methods: We employed a multi-faceted approach to analyze immune responses post-WET, including assessments of gross changes in corneal transparency, thickness, and skin condition. Histopathological examinations of both ocular and surrounding skin tissues provided insights into cellular changes, complemented by ocular RT-qPCR for molecular analysis. Serological analysis was employed to quantify cytokines, chemokines, and donor-specific antibodies, aiming to identify potential biomarkers correlating with WET rejection and to validate the presence of antibody-mediated rejection. These methodologies collectively contribute to the development of non-invasive diagnostic and monitoring strategies for WET.

Results: Our study revealed a rapid and acute immune response following WET, characterized by an early innate immune response dominated by complement involvement, and infiltration of neutrophils and monocytes by post-operative day (POD) 2. This was succeeded by an acute T-cell-mediated immune reaction, predominantly involving T helper 1 (Th1) cells and cytotoxic T lymphocytes (CTLs). The presence of donor specific antibody (DSA) and indications of pyroptosis in the early phases of rejection were observed. Notably, the early elevation of serum CXCL10 by POD4, coupled with ocular CD3+ cell infiltration, emerged as a potential early biomarker for WET rejection. Additionally, corneal transparency grading proved effective as a non-invasive monitoring tool.

Conclusion: This study offers a first-time comprehensive exploration of immune responses in WET, unveiling rapid and complex rejection mechanisms. The identification of early biomarkers and the development of non-invasive monitoring techniques significantly advance our understanding of WET rejection. Additionally, these findings establish an essential baseline for future research in this evolving field.

Keywords

Animals, Graft Rejection, Rats, Corneal Transplantation, Biomarkers, Male, Cytokines, Disease Models, Animal, whole eye transplantation, vascularized composite allotransplantation, immune rejection, diagnostic strategies, monitoring techniques, non-invasive biomarkers

Published Open-Access

yes

Recommended Citation

Li, Bing; Wang, Yong; Owens, Charles R; et al., "Immune Responses in Rodent Whole Eye Transplantation: Elucidation and Preliminary Investigations Into Rejection Diagnosis and Monitoring" (2025). Faculty, Staff and Student Publications. 6077.
https://digitalcommons.library.tmc.edu/uthgsbs_docs/6077