Immune responses in rodent whole eye transplantation: elucidation and preliminary investigations into rejection diagnosis and monitoring
BackgroundWhole 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 re...
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Frontiers Media S.A.
2025-01-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1475055/full |
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| author | 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 |
| author_facet | 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 |
| author_sort | Bing Li |
| collection | DOAJ |
| description | BackgroundWhole 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.MethodsWe 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.ResultsOur 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.ConclusionThis 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. |
| format | Article |
| id | doaj-art-b32e1df2288e41f6833d0b00f98ebffd |
| institution | Kabale University |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Immunology |
| spelling | doaj-art-b32e1df2288e41f6833d0b00f98ebffd2025-01-29T06:45:56ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-01-011610.3389/fimmu.2025.14750551475055Immune responses in rodent whole eye transplantation: elucidation and preliminary investigations into rejection diagnosis and monitoringBing Li0Yong Wang1Charles R. Owens2Touka Banaee3Charleen T. Chu4Kayvon Jabbari5Anna D. Lee6Neil J. Khatter7Alan G. Palestine8An-Jey A. Su9Christene A. Huang10Kia M. Washington11Division of Plastic Surgery, Department of Surgery, University of Colorado Anschutz Medical Campus, Aurora, CO, United StatesDivision of Plastic Surgery, Department of Surgery, University of Colorado Anschutz Medical Campus, Aurora, CO, United StatesDivision of Plastic Surgery, Department of Surgery, University of Colorado Anschutz Medical Campus, Aurora, CO, United StatesDepartment of Ophthalmology and Visual Sciences, University of Texas Medical Branch, Galveston, TX, United StatesDepartment of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA, United StatesDivision of Plastic Surgery, Department of Surgery, University of Colorado Anschutz Medical Campus, Aurora, CO, United StatesDivision of Plastic Surgery, Department of Surgery, University of Colorado Anschutz Medical Campus, Aurora, CO, United StatesDivision of Plastic Surgery, Department of Surgery, University of Colorado Anschutz Medical Campus, Aurora, CO, United StatesSue Anschutz-Rogers Eye Center, Department of Ophthalmology, University of Colorado Anschutz Medical Campus, Aurora, CO, United StatesDivision of Plastic Surgery, Department of Surgery, University of Colorado Anschutz Medical Campus, Aurora, CO, United StatesDivision of Plastic Surgery, Department of Surgery, University of Colorado Anschutz Medical Campus, Aurora, CO, United StatesDivision of Plastic Surgery, Department of Surgery, University of Colorado Anschutz Medical Campus, Aurora, CO, United StatesBackgroundWhole 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.MethodsWe 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.ResultsOur 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.ConclusionThis 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.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1475055/fullwhole eye transplantationvascularized composite allotransplantationimmune rejectiondiagnostic strategiesmonitoring techniquesnon-invasive biomarkers |
| spellingShingle | 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 Immune responses in rodent whole eye transplantation: elucidation and preliminary investigations into rejection diagnosis and monitoring Frontiers in Immunology whole eye transplantation vascularized composite allotransplantation immune rejection diagnostic strategies monitoring techniques non-invasive biomarkers |
| title | Immune responses in rodent whole eye transplantation: elucidation and preliminary investigations into rejection diagnosis and monitoring |
| title_full | Immune responses in rodent whole eye transplantation: elucidation and preliminary investigations into rejection diagnosis and monitoring |
| title_fullStr | Immune responses in rodent whole eye transplantation: elucidation and preliminary investigations into rejection diagnosis and monitoring |
| title_full_unstemmed | Immune responses in rodent whole eye transplantation: elucidation and preliminary investigations into rejection diagnosis and monitoring |
| title_short | Immune responses in rodent whole eye transplantation: elucidation and preliminary investigations into rejection diagnosis and monitoring |
| title_sort | immune responses in rodent whole eye transplantation elucidation and preliminary investigations into rejection diagnosis and monitoring |
| topic | whole eye transplantation vascularized composite allotransplantation immune rejection diagnostic strategies monitoring techniques non-invasive biomarkers |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1475055/full |
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