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Kathryn Paunicka, Peter W. Chen, Jerry Y. Niederkorn; Penetrating Keratoplasty To One Eye Abolishes Immune Privilege For Corneal Allografts Placed Into The Other Eye. Invest. Ophthalmol. Vis. Sci. 2012;53(14):2384.
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Determine the effect penetrating keratoplasty and corneal surgery on the immune privilege of subsequent corneal allografts.
Fully allogeneic corneal allografts (C57BL/6 H-2b) or syngeneic corneal grafts (BALB/c H-2b) were transplanted orthotopically to BALB/c mice that had previously rejected a third party allograft (C3H H-2k) or had accepted a syngeneic graft. The loss of local and systemic immune privilege was examined by assessing the incidence and tempo of rejection of C57BL/6 grafts. Other experiments evaluated the effect of performing a 360 degree corneal incision in the right eye and evaluating the fate of corneal allografts placed into the left eye. The loss of systemic immune privilege was examined by assessing the rejection status of the C57BL/6 graft placed onto the unmanipulated contralateral eye.
First time C57BL/6 corneal allografts consistently underwent rejection in 50% of the hosts (N=10). By contrast, rejection of a C3H allograft prior to the application of a subsequent C57BL/6 corneal allograft into the same eye resulted in 100% graft rejection of the C57BL/6 corneal allografts (N=18, P <0.001). Importantly, C57BL/6 corneal allografts placed into the left eyes of BALB/c mice that had rejected a C3H allograft in the right eye resulted in 100% rejection of the C57BL/6 corneal allografts (N=12, P < 0.001). Acceptance of a BALB/c syngeneic graft exacerbated graft rejection of C57BL/6 corneal allografts that were grafted to the same eye (N =12, P< 0.001) or even to the unmanipulated contralateral eye (N =8, P = 0.048). Performing a 360 circumferential incision to the corneal surface of the right eye resulted in 100% rejection of the C57BL/6 corneal allograft placed onto the left eye (N = 19, P < 0.001).
Penetrating keratoplasty, even in the form of a syngeneic corneal graft abolishes immune privilege in the manipulated eye and even in the contralateral eye that was not subjected to keratoplasty. Moreover, a simple 360 degree corneal incision in one eye robs the contralateral eye of its immune privilege and leads to 100% graft rejection. These findings suggest that surgery to the ocular surface evokes a sympathetic loss of immune privilege in the contralateral eye that is most likely elicited by a neurogenic signal originating in the severed corneal nerves. These results may also shed light on the heightened incidence of corneal allograft rejection that has been reported in patients who receive a second corneal allograft from a presumably unrelated donor who does not share the same array of histocompatibility antigens as those found on the first graft.
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