September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
Long term Effect of anti-CD40 antibody treatment on the survival of corneal xenotransplantation
Author Affiliations & Notes
  • Mee Kum Kim
    Ophthalmology, Seoul National University College of Medicine, Seoul, Korea (the Republic of)
    Laboratory of Ocular Regenerative Medicine and Immunology, Seoul National University Hospital Biomedical Research Institute, Seoul, Korea (the Republic of)
  • Jaeyoung Kim
    Ophthalmology, Seoul National University College of Medicine, Seoul, Korea (the Republic of)
  • Dong Hyun Kim
    Ophthalmology, Seoul National University College of Medicine, Seoul, Korea (the Republic of)
  • Hyuk Jin Choi
    Ophthalmology, Seoul National University College of Medicine, Seoul, Korea (the Republic of)
  • Hyun Ju Lee
    Laboratory of Ocular Regenerative Medicine and Immunology, Seoul National University Hospital Biomedical Research Institute, Seoul, Korea (the Republic of)
  • Hyun Jeong Jeong
    Laboratory of Ocular Regenerative Medicine and Immunology, Seoul National University Hospital Biomedical Research Institute, Seoul, Korea (the Republic of)
  • Hee Jung Kang
    Laboratory Medicine, Hallym University College of Medicine, Anyang, Korea (the Republic of)
  • Chung-Gyu Park
    Microbiology and Immunology, Seoul National University College of Medicine, Seoul, Korea (the Republic of)
  • Won Ryang Wee
    Ophthalmology, Seoul National University College of Medicine, Seoul, Korea (the Republic of)
    Laboratory of Ocular Regenerative Medicine and Immunology, Seoul National University Hospital Biomedical Research Institute, Seoul, Korea (the Republic of)
  • Footnotes
    Commercial Relationships   Mee Kum Kim, None; Jaeyoung Kim, None; Dong Hyun Kim, None; Hyuk Jin Choi, None; Hyun Ju Lee, None; Hyun Jeong Jeong, None; Hee Jung Kang, None; Chung-Gyu Park, None; Won Ryang Wee, 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 September 2016, Vol.57, 1440. doi:
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      Mee Kum Kim, Jaeyoung Kim, Dong Hyun Kim, Hyuk Jin Choi, Hyun Ju Lee, Hyun Jeong Jeong, Hee Jung Kang, Chung-Gyu Park, Won Ryang Wee; Long term Effect of anti-CD40 antibody treatment on the survival of corneal xenotransplantation
      . Invest. Ophthalmol. Vis. Sci. 2016;57(12):1440.

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      © 2017 Association for Research in Vision and Ophthalmology.

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Abstract

Purpose : Previous study shows anti-CD154 (CD40 ligand) treatment, as an inhibitor of CD40 ligand, is effective on corneal xenotransplantation, however, anti-CD154 treatment can not be used in human clinical trial due to thromboembolism. To investigate the effect of systemically administered anti-CD40 antibodies on the survival of deep lamellar porcine corneal grafts in pig-to-rhesus corneal transplantation model.

Methods : Five Chinese rhesus macaques underwent deep lamellar corneal transplantation with clinically acceptable sized (7.5 mm in diameter) wild-type porcine corneal grafts using big bubble technique. Intravenous anti-CD40 antibodies (Abs) (30-50 mg/kg, x15/6 months) and immunoglobulin were administered as programmed schedule. Rejection sign, central corneal thickness, and recipients’ immunologic profile including memory T cells, anti-α-Gal and donor-specific Abs, and aqueous complement concentration were evaluated. Cellular infiltration into the xenografts was evaluated by immunohistochemical staining. Immunologic profiles in anti-CD40 Abs-treated groups were compared with those in in anti-CD154 Abs-treated groups in our previous report.

Results : Anti-CD 40 Abs-based immunosuppressive treatment achieved the successful survival of xenocorneal grafts (389 days, 382 days, 236 days, 201 days, >61 days) without any ocular complications. Levels of central memory or effector memory CD8+ or CD4+ T cells in anti-CD40 Abs-treated primates were not significantly different from those in anti-CD154 Abs-treated primates. Levels of donor-specific Ig G and Ig M levels, levels of anti alpha-Gal Ig G and Ig M, and non- alpha-Gal Ig G in the blood, and level of complement in aqueous humor were not increased. Histology showed that CD3+ T cells or macrophages were not found in anti-CD40 Abs-treated grafts.

Conclusions : Treatment of anti-CD40 Abs achieved long-term success on the survival of corneal deep lamellar xenotransplantation, and the effect of anti-CD40 Abs treatment appears to be comparable to the effect of Anti-CD154 Abs treatment on corneal xenotransplantation.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.

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