June 2017
Volume 58, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2017
Application of mesenchymal stromal cells modulates corneal allograft rejection in a pre-sensitised high risk cornea transplantation model
Author Affiliations & Notes
  • Paul Lohan
    Regenerative Medicine Institute, National University of Ireland, Galway, Galway, Ireland
  • Oliver Treacy
    Regenerative Medicine Institute, National University of Ireland, Galway, Galway, Ireland
  • Mourice Morcos
    Regenerative Medicine Institute, National University of Ireland, Galway, Galway, Ireland
  • Nick Murphy
    Regenerative Medicine Institute, National University of Ireland, Galway, Galway, Ireland
  • Gerry Fahy
    Galway University Hospital, Galway, Ireland
  • Matthew D Griffin
    Regenerative Medicine Institute, National University of Ireland, Galway, Galway, Ireland
  • Thomas Ritter
    Regenerative Medicine Institute, National University of Ireland, Galway, Galway, Ireland
  • Footnotes
    Commercial Relationships   Paul Lohan, None; Oliver Treacy, None; Mourice Morcos, None; Nick Murphy, None; Gerry Fahy, None; Matthew Griffin, None; Thomas Ritter, None
  • Footnotes
    Support  EU FP7 VISICORT grant
Investigative Ophthalmology & Visual Science June 2017, Vol.58, 987. doi:
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      Paul Lohan, Oliver Treacy, Mourice Morcos, Nick Murphy, Gerry Fahy, Matthew D Griffin, Thomas Ritter; Application of mesenchymal stromal cells modulates corneal allograft rejection in a pre-sensitised high risk cornea transplantation model. Invest. Ophthalmol. Vis. Sci. 2017;58(8):987.

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

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Abstract

Purpose : Corneal transplant rejection in patients at high immunological risk of rejection due to previous grafts or other immune sensitisation events represents a significant unmet medical need. We sought to establish a rat model of previous immunological sensitisation to the cornea donor. Once established we used this model to study the effects of mesenchymal stromal cells (MSC) on the rejection process in a high risk setting.

Methods : Pre-existing anti-donor immunity was induced in Lewis rats (LEW, RT-1l) by injecting 1 X 107 donor (Dark Agouti (DA, RT-1avl)) derived rat splenocytes subcutaneously 14 days prior to performing penetrating full thickness keratoplasty using a DA cornea as the donor tissue. Graft rejection was determined by corneal opacification, with edema and neovascularisation also recorded. Allogeneic donor-derived and 3rd party (fully allogeneic to both corneal donor and recipient) MSC were isolated from rat bone marrow, cultured and characterised in vitro. 1 X 106 MSC were injected at day -7 and day -1 intravenously. The effects of MSC treatment on the rejection process were recorded. Comparison of the graft survival of untreated, allogeneic MSC treated and 3rd party MSC treated were compared using Mantel-Cox tests.

Results : MSC were shown to possess tri-lineage differentiation capabilities and were capable of significantly suppressing Lewis T cell proliferation in vitro. Rats pre-sensitised with donor (DA) splenocytes rejected their grafts earlier (n=13, average day of rejection (ADR) 11.45±2.5) than those which were not pre-sensitised (n=17, ADR 18.24±3.15). Donor derived MSC were shown to be capable of significantly prolonging corneal allograft survival (n=10, ADR 22±8.01) (p=0.0002). Indeed 40% of animals treated with allogeneic MSC had not rejected their grafts by the end of the observation period at day 30.

Conclusions : To date, a high risk model of rat cornea transplantation involving a strong pre-existing anti-donor response has been developed and proved to be reproducible across several groups. MSC have been shown to be efficacious in modulating the immune response against the graft, resulting in prolonged graft survival. Further experiments will probe the mechanism of action of allogeneic MSC in this high-risk model.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.

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