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L. Kuffova, A. Guo, E. Muckersie, M. Robertson, V. Holá&, J.V. Forrester; Prior Graft Rejection by Either Direct or Indirect Allorecognition Are Equal High Risk Factors for Rejection of a Second Corneal Graft . Invest. Ophthalmol. Vis. Sci. 2006;47(13):1303.
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Graft rejection is recognised to be the major cause of corneal graft failure in humans. This study was undertaken to compare the effects of two different modes of "high–risk" allosensitisation, direct allosensitisation via prior skin grafting and indirect allosensitisation via a first corneal graft on the outcome of a second corneal graft using the same fully mis–matched combinations.
Two models of corneal "high–risk" recipient were established (a) a corneal presensitisation model in which a second corneal graft was placed in the same eye of a mouse which had previously received a corneal allograft of the same major and minor MHC mismatch combination (C57BL/6 to Balb/c); (b) a skin presensitisation model in which a skin allografts was performed two weeks prior to corneal allograft also using the same strain combination. The corneal grafts were observed for 6–8 weeks and graft survival compared with graft rejection rates in primary allograft strain combination.
Presensitisation via prior skin or prior corneal grafting led to accelerated and maximum (100%) risk of second graft rejection provided the first graft was also rejected (MST 11.1 days with prior skin graft and MST 7.5 days with prior corneal graft compared to 13.8 days for first graft into non–sensitised host). However, if the first corneal graft was accepted, then the risk of rejection with the same strain combination was reduced (MST 8.5 days for prior accepted graft vs. MST 6.8 for prior rejected grafts) although the overall incidence of rejection remained 100% compared to 45% in naïve recipients. Prior skin or corneal graft rejection was not a risk factor for acceptance of a second syngeneic corneal graft, indicating that accelerated graft rejection of second corneal grafts was due exclusively to presensitisation and not to the trauma of the initial procedure.
Presensitisation of the host through direct (skin) or indirect (cornea) allosensitisation were equal risk factors for failure of a second corneal graft provided the first graft was rejected. The risk was reduced if the first corneal graft was accepted suggesting that tolerance to allografts through presensitisation might be possible via indirect allorecognition.
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