Prognostic factor analysis for xenocorneal anterior lamellar transplantation using genetically-modified pig
Sun Ae Hwang1, Kyoung Sik Park1, Wan Seop Kim2, Hyunil Kim3, Jeong Ho Hwang4, Yu Rim Ahn5, Eun Yeol Yang1, IK Jin Yun1, Ki Cheul Shin5.
1Department of Surgery, Konkuk University School of Medicine, Seoul, Korea; 2Dapartment of Pathology, Konkuk University School of Medicine, Seoul, Korea; 3Department of Transgenic Animal Research, Optipharm, Cheongju-si, Korea; 4Large Animals Convergence Research, Korea Institute of Toxicology Center , Jeongeup-si, Korea; 5Department of Ophthalmology, Konkuk University School of Medicine, Seoul, Korea
Introduction: Xenocorneal transplantation has emerged as a promising alternative to address the global shortage of corneal donors. This study analyzes prognostic factors influencing survival rates in xenocorneal anterior lamellar transplantation using a genetically modified pig to non human primate.
Methods: In this study, various gene-modified pig corneas were used, including GTKO (α1,3-galactosyltransferase gene-knockout; n=1), GTKO/CD46 (n=10), GTKO/CD46/CD73 (n=2), GTKO/CD46/TBM (Thrombomodulin; n=3), TKO (GGTA1/CMAH/B4GalNT2; n=1), TKO/CD46/TBM (n=1), and QKO (TKO+iGb3S)/CD46/TBM (n=2). For minimal immunosuppression, a subconjunctival injection of dexamethasone (1.5 mg/0.3 mL) was administered, together with 0.5% levofloxacin and 1% prednisolone acetate eye drops for two months. If signs of rejection, such as graft edema or initial corneal opacity, were observed, the initial immunosuppressive regimen was re-administered. The occurrence and timing of rejection, as well as the graft survival period after rejection, were compared by dividing the subjects into long-term and short-term survival groups. Histopathological analysis was also performed.
Results
Key findings include:
In this study, consistent long-term survival was not achieved.
Analysis of survival rates in xenogeneic partial-thickness corneal transplantation revealed that the long-term survival group (>180 days) had a mean survival period of 585.33 days (±135.10 days, n=9), while the short-term survival group (<180 days) showed a mean survival period of 51.82 days (±10.45 days, n=11).
The frequency of subconjunctival dexamethasone injections and the pattern of steroid eye drop usage showed an association with graft survival.
In the long-term survival group, initial intensive immunosuppressive therapy and continuous immunosuppression were found to be effective in extending graft survival.
Histopathological analysis confirmed minimized tissue damage in the long-term survival group.
Conclusions: Xenocorneal anterior lamellar transplantation using genetically-modified pig demonstrates clinical potential. However, to achieve consistent long-term survival further genetic modifications, optimized immunosuppressive protocols, and deeper understanding of survival mechanisms is required.
: This work was supported by the Korea Health Industry Development Institute (KHIDI) [grant number RS-2023-KH136889]. .
[1] Xenocorneal Anterior Lamellar Transplantation
[2] Genetically modified pig to non-human primate
[3] Minimal immunosuppression
[4] Prognostic Factor Analysis
[5] Long-term survival (>180 days) and short-term survival (<180 days)
[6] Graft survival