Journal Mobile Options
Table of Contents
Vol. 47, No. 1, 2012
Issue release date: December 2011
Ophthalmic Res 2012;47:39–46

A Decrease in the Density of HLA-DR-Positive Cells Occurs Faster in Corneas Stored in Organ Culture than under Hypothermic Conditions

Al-Fakih A. · Faltus V. · Jirsova K.
aLaboratory of the Biology and Pathology of the Eye, Institute of Inherited Metabolic Disorders, and bOcular Tissue Bank, General Teaching Hospital and First Faculty of Medicine, Charles University in Prague, and cEuroMISE Center, Department of Medical Informatics, Institute of Computer Sciences AS CR, Prague, Czech Republic

Individual Users: Register with Karger Login Information

Please create your User ID & Password

Contact Information

I have read the Karger Terms and Conditions and agree.

To view the fulltext, please log in

To view the pdf, please log in


Aims: To compare the number of antigen-presenting cells (APC) at various locations in fresh human corneoscleral disks and in those that are stored for grafting under hypothermic conditions or in organ culture (OC) with the aim of determining the conditions under which the decline in APC numbers is most substantial. Methods: Cryosections obtained from fresh corneoscleral disks and disks stored under hypothermic (Optisol-GS) or OC conditions were used. The density of HLA-DR-positive cells was determined on cross sections using enzyme immunohistochemistry (alkaline phosphatase-antialkaline phosphatase technique). Longitudinal sections were used for detecting ATPase activity. Results: The densities of HLA-DR-positive cells in both the epithelium and stroma increased from the central (3.79 and 0.61/mm2) to the peripheral cornea (5.56 and 1.35/mm2) as well as to the limbus and conjunctiva. A marked decrease in the number of HLA-DR-positive cells occurred after 7 days of storage in all corneal areas, the limbus and conjunctiva, compared to fresh tissue. No positive cells were found in the epithelium of corneas after 14 days in OC and after 21 days in hypothermic storage. Twenty-eight days of storage in OC led to the complete absence of HLA-DR-positive cells in the epithelium of the limbus and conjunctiva, and to a significant reduction in the stroma. Conclusion: Corneas stored in OC longer than 14 days are likely to be less immunogenic than corneas stored under hypothermic conditions, thus resulting in a possible positive effect on prolonging graft survival.

Copyright / Drug Dosage

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.


  1. Pepose JS, Gardner KM, Nestor MS, Foos RY, Pettit TH: Detection of HLA class I and II antigens in rejected human corneal allografts. Ophthalmology 1985;92:1480–1484.
  2. Niederkorn JY, Ross JR, He Y: Effect of donor Langerhans cells on corneal graft rejection. J Invest Dermatol 1992;99:104S–106S.
  3. Dana MR, Qian Y, Hamrah P: Twenty-five-year panorama of corneal immunology: emerging concepts in the immunopathogenesis of microbial keratitis, peripheral ulcerative keratitis, and corneal transplant rejection. Cornea 2000;19:625–643.
  4. Gillette TE, Chandler JW, Greiner JV: Langerhans cells of the ocular surface. Ophthalmology 1982;89:700–711.
  5. McCallum RM, Cobo LM, Haynes BF: Analysis of corneal and conjunctival microenvironments using monoclonal antibodies. Invest Ophthalmol Vis Sci 1993;34:1793–1803.
  6. Vantrappen L, Geboes K, Missotten L, Maudgal PC, Desmet V: Lymphocytes and Langerhans cells in the normal human cornea. Invest Ophthalmol Vis Sci 1985;26:220–225.
  7. Williams KA, Roder D, Esterman A, Muehlberg SM, Coster DJ: Factors predictive of corneal graft survival: report from the Australian Corneal Graft Registry. Ophthalmology 1992;99:403–414.
  8. Huq S, Liu Y, Benichou G, Dana MR: Relevance of the direct pathway of sensitization in corneal transplantation is dictated by the graft bed microenvironment. J Immunol 2004;173:4464–4469.
  9. Hamrah P, Huq SO, Liu Y, Zhang Q, Dana MR: Corneal immunity is mediated by heterogeneous population of antigen-presenting cells. J Leukoc Biol 2003;74:172–178.
  10. Yamagami S, Usui T, Amano S, Ebihara N: Bone marrow-derived cells in mouse and human cornea. Cornea 2005;24:S71–S74.
  11. Mayer WJ, Irschick UM, Moser P, Wurm M, Huemer HP, Romani N, Irschick EU: Characterization of antigen-presenting cells in fresh and cultured human corneas using novel dendritic cell markers. Invest Ophthalmol Vis Sci 2007;48:4459–4467.
  12. Pels E, van der Gaag R: HLA-A,B,C, and HLA-DR antigens and dendritic cells in fresh and organ culture preserved corneas. Cornea 1984;3:231–239.
  13. Girolomoni G, Santantonio ML, Pastore S, Bergstresser PR, Giannetti A, Cruz PD Jr: Epidermal Langerhans cells are resistant to the permeabilizing effects of extracellular ATP: in vitro evidence supporting a protective role of membrane ATPase. J Invest Dermatol 1993;100:282–287.
  14. Baggesen K, Lamm LU, Ehlers N: Significant effect of high-resolution HLA-DRB1 matching in high-risk corneal transplantation. Transplantation 1996;62:1273–1277.
  15. European Eye Bank Association: European Eye Bank Association Directory, ed 18. Barcelona, European Eye Bank Association, 2010.
  16. Bergstresser PR, Toews GB, Streilein JW: Natural and perturbed distributions of Langerhans cells: responses to ultraviolet light, heterotopic skin grafting, and dinitrofluorobenzene sensitization. J Invest Dermatol 1980;75:73–77.
  17. Ingham E, Matthews JB, Kearney JN, Gowland G: The effects of variation of cryopreservation protocols on the immunogenicity of allogeneic skin grafts. Cryobiology 1993;30:443–458.
  18. Jacobs BB: Ovarian allograft survival: prolongation after passage in vitro. Transplantation 1974;18:454–457.
  19. Lafferty KJ, Bootes A, Dart G, Talmage DW: Effect of organ culture on the survival of thyroid allografts in mice. Transplantation 1976;22:138–149.
  20. Simon M, Fellner P, El-Shabrawi Y, Ardjomand N: Influence of donor storage time on corneal allograft survival. Ophthalmology 2004;111:1534–1538.
  21. Holland EJ, DeRuyter DN, Doughman DJ: Langerhans cells in organ-cultured corneas. Arch Ophthalmol 1987;105:542–545.
  22. Ardjomand N, Berghold A, Reich ME: Loss of corneal Langerhans cells during storage in organ culture medium, Optisol and McCarey-Kaufman medium. Eye (Lond) 1998;12:134–138.
  23. Pérez-Torres A, Ustarroz-Cano M, Millán-Aldaco D: Langerhans cell-like dendritic cells in the cornea, tongue and oesophagus of the chicken (Gallus gallus). Histochem J 2002;34:507–515.
  24. Pels E, Beekhuis WH, Völker-Dieben HJ: Long-term tissue storage for keratoplasty; in Brightbill FS (ed): Corneal Surgery. Theory, Technique, and Tissue. St Louis, Mosby, 1999, pp 897–906.
  25. Castell-Rodríguez AE, Hernández-Peñaloza A, Sampedro-Carrillo EA, Herrera-Enriquez MA, Alvarez-Pérez SJ, Rondán-Zarate A: ATPase and MHC class II molecules co-expression in Rana pipiens dendritic cells. Dev Comp Immunol 1999;23:473–485.
  26. Igyarto BZ, Lacko E, Olah I, Magyar A: Characterization of chicken epidermal dendritic cells. Immunology 2006;119:278–288.
  27. Shanmuganathan VA, Rotchford AP, Tullo AB, Joseph A, Zambrano I, Dua HS: Epithelial proliferative potential of organ cultured corneoscleral rims: implications for allo-limbal transplantation and eye banking. Br J Ophthalmol 2006;90:55–58.

Pay-per-View Options
Direct payment This item at the regular price: USD 38.00
Payment from account With a Karger Pay-per-View account (down payment USD 150) you profit from a special rate for this and other single items.
This item at the discounted price: USD 26.50