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Jerry Niederkorn, Kathryn Paunicka, Jessamee Mellon; Penetrating keratoplasty to one eye abolishes immune privilege and promotes corneal allograft rejection in the opposite eye, even to grafts from unrelated donors. Invest. Ophthalmol. Vis. Sci. 2013;54(15):2160.
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To determine the effect of penetrating keratoplasty (PK) on immune privilege of subsequent corneal allografts in both eyes.
Corneas from BALB/c, C57BL/6, C3H, or A/J donors were grafted orthotopically to BALB/c mice. A 2 mm trephine was used to make shallow circumferential incisions in left eyes prior to applying corneal allografts to right eyes. Ocular neuropeptide levels were evaluated by enzyme immunoassays. Substance P (SP) was blocked by daily administration of Spantide II (72 micrograms/day).
PK to one eye abolished immune privilege and exacerbated graft rejection in the same eye or the unmanipulated eye. C57BL/6 corneal allografts normally undergo rejection in 50% of BALB/c hosts. However, BALB/c hosts that previously rejected C3H or A/J allografts in the right eye had 100% rejection of genetically unrelated C57BL/6 corneal allografts placed into the left eye (P <0.001). Moreover, syngeneic BALB/c corneal grafts placed in the right eye induced 88% rejection of C57BL/6 allografts placed in the left eye (P = 0.032). Even a 360 degree corneal surface incision in the right eye induced 100% rejection of corneal allografts in the left eye (P < 0.001), but did not affect survival of BALB/c syngeneic grafts (100% survival; P> 0.05). Surgery-induced graft rejection was associated with severing corneal nerves and not due to trauma, as insertion of sutures in the right eye did not affect graft survival in the left eye. Likewise, “X” shaped corneal incisions did not affect graft survival in the other eye (P > 0.05). A trephine incision in one eye induced upregulation of SP in both eyes. Trephine
Circular corneal surface incisions, and not simple ocular trauma (e.g., sutures or “X” shaped incisions), abolish immune privilege in both eyes. Sympathetic abolition of immune privilege is associated with upregulation of SP in the contralateral eye. Blocking SP with Spantide II restores immune privilege and suggests that SP is a key mediator that abolishes immune privilege in response to severing corneal nerves during PK.
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