Effects of Several Genetic Engineering in the Graft Survival of Pig-to-Monkey Lamellar Corneal Xenotransplantation with Minimal Immunosuppression

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Abstract

Purpose

To investigate the graft survival and histologic differences of genetically engineered pigs (1,3-galactosyltransferase gene-knockout [GTKO] pig and pig GTKO with expressing a human complement-regulatory protein [GTKO/CD46]) – to - cynomolgus monkey lamellar corneal xenotransplantation.

Methods

Six cynomolgus monkeys underwent lamellar corneal xenotransplantation from GTKO(1), GTKO/CD46(3) and GTKO/CD46/CD73 pigs. The graft diameter was 7.5mm and thickness was about 300um. For minimal immunosuppression subconjunctival injection of dexamethasone(1.5mg/0.3ml) was done immediate postoperatively and eyedrops of 0.5% levofloxacin and 1% prednisolone acetate were applied 4 times a day for 1 week, gradually tapered and once a day after 1 month. No eyedrops were applied after 3 months. Rejection signs of graft and histology of graft after rejection were evaluated. Graft failure due to rejection was defined as corneal opacity of grade 4 over 2 weeks.

Results

Graft from GTKO pig showed gradual corneal opacity from the 70 days after transplantation and was rejected at day 97. One lamellar corneal transplanted monkey from GTKO/CD46 pig was rejected at day 244. The other two monkeys received corneas from one GTKO/CD46 pig show 6 months survival without rejection now. Two corneas from GTKO/CD46/CD39 pig rejected after 39 days. There were many inflammatory cells in rejected graft and no inflammatory cells in recipient’s stromal bed.

Conclusions

Lamellar xenocorneal transplantation has the advantages of not having surgical complications such as retrocorneal membrane or anterior synechia seen in full thickness corneal xenotransplantation. Genetic engineered pig to cynomolgus lamellar corneal xenotransplantation maybe show long-term graft survival without any aggressive systemic immunosuppression especially in GTKO/CD46 gene engineered pigs in our results. However, which genetic engineering is the fittest should be investigated more.

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