Cross-reactivity of porcine xenocorneal transplantation with allo-corneal transplantation as a temporary bridge in nonhuman primates

Poster Details

First Author: J.Lee SOUTH KOREA

Co Author(s):    J. Lee   H. Lee   A. Ko   H. Choi   M. Kim   W. Wee

Abstract Details

Purpose:

Decellularized porcine xeno-corneal graft had been developed in our lab and 6 months-efficacy of lamellar xenocorneal transplantation was shown in nonhuman primates. To assess the feasibility as a temporal bridge graft, we investigated the cross reactivity against corneal allografts in xenocorneal transplanted nonhuman primates.

Setting:

Preclinical animal study

Methods:

Five Chinese rhesus macaques which received decellularized porcine corneal lamellae and were followed up for at least 6 months underwent full-thickness corneal allotransplantation. Previous xeno-grafts (7.5mm in diameter) were removed with 8.0mm trephines and 8.5mm-sized grafts from donor macaques were transplanted. Clinically applicable minimal immunosuppression was done based on topical, subconjunctival and systemic corticosteroids. Rejection signs and serial changes in recipients’ blood profile, including memory T cell subset, anti-Gal and donor pig–specific antibodies, and complement were evaluated. Changes in aqueous complement concentration were also assessed at 4 weeks after transplantation. The mixed lymphocytes reaction (MLR) was analyzed in three rhesus macaques (KPed rhesus) with clear allografts that survived more than 6 months. MLR was done using peripheral blood mononuclear cells (PBMC). PBMCs from the recipient rhesus and normal rhesus were used as responder cells and PBMCs from donor pigs, random pigs, and random macaques were used as stimulator cells with mitomycin C treatment.

Results:

Of the full-thickness allograft recipients, 60% (n=3) remained transparent for more than 6 months, with normal central corneal thickness and normal intraocular pressure (IOP). Immunologic profiles of the recipients with rejected grafts showed a significant increase in the concentration of aqueous complement and an enhancement of effector memory CD8 T cells after postoperative week 4. However, anti-Gal and donor pig–specific antibodies did not change significantly. There were no hyperacute rejections and no increases in memory T cell subsets during the first month after allotransplantation in all individuals. The donor specific xeno-responses in KPed rhesus were not significantly higher than nonspecific xeno-responses. No significant differences in the nonspecific allo-responses were noted between KPed and normal rhesus.

Conclusions:

Decellularized porcine corneal lamellae seemed not to increase the risk of cross-reactivity between the allo-reaction and the xeno-reaction. Porcine xenocorneal transplantation could be considered as a promising candidate for a bridge to human corneal allotransplantation in an emergency setting such as corneal perforation. FINANCIAL DISCLOSURE?: No