July 2018
Volume 59, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2018
In vitro characteristics and in vivo outcome of α1,3-galactosyltransferase gene-knockout miniature pig cornea in full-thickness corneal xenotransplantation using nonhuman primate
Author Affiliations & Notes
  • Chang Ho Yoon
    Ophthalmology, Seoul National University Hospital, Seoul, Korea (the Democratic People's Republic of)
    Laboratory of Ocular Regenerative Medicine and Immunology, Seoul Artificial Eye Center, Seoul National University Hospital Biomedical Research Institute, Seoul, Korea (the Republic of)
  • Se Hyun Choi
    Ophthalmology, Seoul National University Hospital, Seoul, Korea (the Democratic People's Republic of)
    Laboratory of Ocular Regenerative Medicine and Immunology, Seoul Artificial Eye Center, Seoul National University Hospital Biomedical Research Institute, Seoul, Korea (the Republic of)
  • Hyun Ju Lee
    Laboratory of Ocular Regenerative Medicine and Immunology, Seoul Artificial Eye Center, Seoul National University Hospital Biomedical Research Institute, Seoul, Korea (the Republic of)
  • Hong Pyo Kim
    Laboratory of Ocular Regenerative Medicine and Immunology, Seoul Artificial Eye Center, Seoul National University Hospital Biomedical Research Institute, Seoul, Korea (the Republic of)
  • Hee Jung Kang
    Department of Laboratory Medicine, Hallym University College of Medicine, Seoul, Korea (the Republic of)
  • Jong Min Kim
    Translational Xenotransplantation Research Center, Seoul National University College of Medicine, Seoul, Korea (the Republic of)
  • Hyuk Jin Choi
    Ophthalmology, Seoul National University Hospital, Seoul, Korea (the Democratic People's Republic of)
    Laboratory of Ocular Regenerative Medicine and Immunology, Seoul Artificial Eye Center, Seoul National University Hospital Biomedical Research Institute, Seoul, Korea (the Republic of)
  • Chung-Gyu Park
    Translational Xenotransplantation Research Center, Seoul National University College of Medicine, Seoul, Korea (the Republic of)
    Department of Microbiology and Immunology, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea (the Republic of)
  • Kimyung Choi
    Optipharm, Inc., Seoul, Korea (the Republic of)
  • Hyunil Kim
    Optipharm, Inc., Seoul, Korea (the Republic of)
  • Curie Ahn
    Department of Internal medicine, Seoul National University College of Medicine, Seoul, Korea (the Republic of)
  • Mee Kum Kim
    Ophthalmology, Seoul National University Hospital, Seoul, Korea (the Democratic People's Republic of)
    Laboratory of Ocular Regenerative Medicine and Immunology, Seoul Artificial Eye Center, Seoul National University Hospital Biomedical Research Institute, Seoul, Korea (the Republic of)
  • Footnotes
    Commercial Relationships   Chang Ho Yoon, None; Se Hyun Choi, None; Hyun Ju Lee, None; Hong Pyo Kim, None; Hee Jung Kang, None; Jong Min Kim, None; Hyuk Jin Choi, None; Chung-Gyu Park, None; Kimyung Choi, None; Hyunil Kim, None; Curie Ahn, None; Mee Kum Kim, None
  • Footnotes
    Support  This study was supported by a grant from the Korea Healthcare Technology R&D Project, Ministry for Health & Welfare, Republic of Korea (Project No. HI13C0954).
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 1332. doi:
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      Chang Ho Yoon, Se Hyun Choi, Hyun Ju Lee, Hong Pyo Kim, Hee Jung Kang, Jong Min Kim, Hyuk Jin Choi, Chung-Gyu Park, Kimyung Choi, Hyunil Kim, Curie Ahn, Mee Kum Kim; In vitro characteristics and in vivo outcome of α1,3-galactosyltransferase gene-knockout miniature pig cornea in full-thickness corneal xenotransplantation using nonhuman primate. Invest. Ophthalmol. Vis. Sci. 2018;59(9):1332.

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

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Abstract

Purpose : Recent studies showed α1,3-galactosyltransferase gene-knockout (GTKO) pig corneas were not associated with prolonged full-thickness corneal xenograft survival in nonhuman primates, while the mechanism was not known well. We investigated the biofunctional profiles of GTKO miniature pig cornea and its outcome in pig-to-rhesus full thickness corneal xenotransplantation.

Methods : Ten eyes of GTKO (n=3) and GTKO/CD39 knock-in (n=2) miniature pigs were used to evaluate the physical and functional characteristics. Five Chinese rhesus macaques underwent full thickness corneal xenotransplantation (mean donor age: 11.3 mo). Systemic tacrolimus, basiliximab, and IVIG were administered as programmed schedules. T cell subsets, anti-αGal, and non-αGal antibodies (Ab) in the blood, and C3a levels in aqueous humor (AH) were evaluated. The results were compared with those of the wild type miniature pig corneal grafted group (n = 4, all grafts survived > 24 weeks, using anti-CD154 Ab) as controls.

Results : Mean central corneal thickness was 763 μm, and the Na+/K+-ATPase was well expressed 7 days after preservation. Mean endothelial cell density was 4729/mm2, and was well maintained >2800/mm2 through 7 days. Mean doubling time was 30.4 hour which was comparable to that in SNU miniature pigs (30.7 hour, P=0.413). The median graft survival was 72 days. Regulatory T cells at rejection decreased from baseline (p=0.043) and were lower than those of controls at postoperative 24 weeks (p=0.014), however the other T cell subsets did not change. Anti-αGal Ab did not increase during the follow-up. At rejection, anti-non-αGal Ab increased from baseline (p=0.043). C3a in AH at postoperative 4 weeks and at rejection increased from baseline (all p=0.043). At postoperative 4 weeks, mean AH and plasma C3a concentrations were higher than those of controls (p=0.016 and 0.036, respectively).

Conclusions : The biofunctional characteristics of GTKO miniature pig cornea are feasible for corneal xenotransplantation. Rejection of GTKO pig-to-rhesus full-thickness corneal xenotransplantation is related with non-αGal Ab, complement and decrease of regulatory T cells. Addition of B cell suppressing regimen should be considered.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.

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