June 2022
Volume 63, Issue 7
Open Access
ARVO Annual Meeting Abstract  |   June 2022
Immunological Response Following Whole Eye Transplantation In A Rat Model
Author Affiliations & Notes
  • An-Jey Su
    Department of Surgery, Division of Plastic and Reconstructive Surgery, University of Colorado - Anschutz Medical Campus, Aurora, Colorado, United States
  • Bing Li
    Department of Surgery, Division of Plastic and Reconstructive Surgery, University of Colorado - Anschutz Medical Campus, Aurora, Colorado, United States
  • Yong Wang
    Department of Surgery, Division of Plastic and Reconstructive Surgery, University of Colorado - Anschutz Medical Campus, Aurora, Colorado, United States
  • Charles R Owens
    Department of Surgery, Division of Plastic and Reconstructive Surgery, University of Colorado - Anschutz Medical Campus, Aurora, Colorado, United States
  • Touka Banaee
    The University of Texas Medical Branch at Galveston, Galveston, Texas, United States
  • Neil J Khatter
    Department of Surgery, Division of Plastic and Reconstructive Surgery, University of Colorado - Anschutz Medical Campus, Aurora, Colorado, United States
  • Anna D Lee
    Department of Surgery, Division of Plastic and Reconstructive Surgery, University of Colorado - Anschutz Medical Campus, Aurora, Colorado, United States
  • David Mathes
    Department of Surgery, Division of Plastic and Reconstructive Surgery, University of Colorado - Anschutz Medical Campus, Aurora, Colorado, United States
  • Evan Farkash
    Pathology, University of Michigan Medical School, Ann Arbor, Michigan, United States
  • Charleen T Chu
    Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States
  • Christene Huang
    Department of Surgery, Division of Plastic and Reconstructive Surgery, University of Colorado - Anschutz Medical Campus, Aurora, Colorado, United States
  • Kia M Washington
    Department of Surgery, Division of Plastic and Reconstructive Surgery, University of Colorado - Anschutz Medical Campus, Aurora, Colorado, United States
  • Footnotes
    Commercial Relationships   An-Jey Su None; Bing Li None; Yong Wang None; Charles Owens None; Touka Banaee None; Neil Khatter None; Anna Lee None; David Mathes None; Evan Farkash None; Charleen Chu None; Christene Huang None; Kia Washington None
  • Footnotes
    Support  Department of Defense Joint Warfighter Medical Research Program W81XWH-16-1-0775
Investigative Ophthalmology & Visual Science June 2022, Vol.63, 958 – A0427. doi:
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    • Get Citation

      An-Jey Su, Bing Li, Yong Wang, Charles R Owens, Touka Banaee, Neil J Khatter, Anna D Lee, David Mathes, Evan Farkash, Charleen T Chu, Christene Huang, Kia M Washington; Immunological Response Following Whole Eye Transplantation In A Rat Model. Invest. Ophthalmol. Vis. Sci. 2022;63(7):958 – A0427.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Distinct from other vascularized composite allotransplantation (VCA), whole eye transplantation (WET) potentially disrupts the blood ocular barrier which could result in increased ocular immunogenicity and associated pathogenesis. We performed orthotopic rodent WET without immunosuppression to assess the immune reaction and rejection response following WET.

Methods : Male 14-16-week-old Lewis (LEW) Allogeneic or Brown Norway (BN) Syngeneic recipients received hemiface/eye grafts from donor BN rats. Changes in graft skin, eye appearance, serum cytokines, ocular tissue gene expression, and histology (Allo=36, Syn=21) were assessed at cross sectional time-points. Longitudinal assessment (Allo=5, Syn=5) was done for corneal thickness by ocular coherence tomography and serum anti-donor specific antibodies (DSA) by flow cytometry. Skin and cornea rejection grades were assigned using the modified Banff VCA scoring system and clinical corneal transplantation scoring. Eyes were stained with hematoxylin and eosin (H&E) and CD3+ T cells were stained by immunohistochemistry. Serum chemokine levels were measured by Luminex and anti-donor antibody responses were detected by flow cytometry.

Results : Corneal rejection scores were higher in Allo vs. Syn group at POD4 (P<0.01). Corneal thickness in the Allo group was 2-fold greater (P<0.01) than the Syn group on POD6. H&E revealed Allo lymphocyte infiltrate increased with time in the eye, suggesting graded rejection. qPCR revealed significant upregulation of transplant rejection-associated genes, mirroring the observed infiltration in histology. Allo serum CXCL10 significantly increased by POD4. IFN-γ increased on POD5. Comparing DSA before and after WET showed that Allo eyes increased in IgM on POD4 (P<0.05) with a peak at POD5 (P<0.0001); IgG appeared at POD6 (P<0.05), increasing until POD8. Banff scores showed a difference between Allo and Syn skin at POD5 (P=0.02).

Conclusions : Our results suggest that allogeneic WET rejection occurs rapidly without immunosuppression, despite the immune privilege potential of the eye. Corneal transparency and serum CXCL10 level increases are early signs of rejection. IFN-γ and Anti-donor IgM increase reflected ongoing rejection. Skin rejection following WET was consistent with other skin containing VCA models. Since the cornea rejects before the skin, it should receive priority as a diagnostic indicator for WET rejection.

This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.

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