Premium
Novel therapeutic strategies for the induction of tolerance in corneal transplantation
Author(s) -
RITTER T,
TREACY O,
O'FLYNN L,
WILK M,
MORCOS M,
RYAN A,
NOSOV M
Publication year - 2012
Publication title -
acta ophthalmologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.534
H-Index - 87
eISSN - 1755-3768
pISSN - 1755-375X
DOI - 10.1111/j.1755-3768.2012.2744.x
Subject(s) - ex vivo , corneal transplantation , transplantation , medicine , immune system , mesenchymal stem cell , immunology , in vivo , transplant rejection , stem cell , cancer research , biology , surgery , pathology , microbiology and biotechnology
Purpose To develop novel treatment protocols for the prolongation of corneal allograft survival. Methods Genetic manipulation of donor corneas prior to transplantation is an attractive approach to protect the graft from allogeneic rejection. A lentiviral construct which encodes for Programmed Death‐Ligand 1 (PD‐L1) was applied for ex‐vivo genetic modification of corneal grafts before transplantation. Moreover, the generation and application of regulatory cell populations such as mesenchymal stem cells (MSCs) and tolerogenic dendritic cells (tolDCs) to modulate immune‐mediated rejection in transplanted animals and their mechanism of action will be discussed in this presentation. Results Overexpression of PD‐L1 in ex‐vivo cultured corneas prior to transplantation significantly prevents corneal allograft rejection by modulating both innate and adaptive intra‐graft allo‐immune responses. Moreover, systemic injection of MSCs and tolDCs is able to prolong corneal allograft survival and reduces neovascularisation and graft opacity. A significant reduction of graft‐infiltrating inflammatory cells was also recorded for both applications. Conclusion Local overexpression of immunomodulatory molecules is a promising approach to prevent corneal graft rejection. In addition treatment of transplanted animals with regulatory cells also modulates corneal allograft survival. These novel therapies may have the potential to be further developed towards a clinical application. [Supported by Science Foundation of Ireland (SFI 07/IN.1/B925). TR is supported by a Travel Grant from Millennium Research Funds, National University of Ireland, Galway]