Local Immunosuppression in Wuzhishan Pig to Rhesus Monkey Descemet's Stripping Automated Endothelial Keratoplasty: An Innovative Method to Promote the Survival of Xenografts

Ophthalmic Res. 2022;65(2):196-209. doi: 10.1159/000521193. Epub 2021 Dec 13.

Abstract

Introduction: Corneal xenotransplantation is an effective solution for human corneal shortage. We investigated the feasibility and efficacy of different postoperative protocols on xeno-Descemet's stripping automated endothelial keratoplasty (DSAEK) grafts.

Methods: Thirty rhesus monkeys were randomly divided into three groups: control group (C) and only Descemet's membrane (DM) stripping, DSAEK 1 (D1) and DSAEK 2 (D2) groups, DM stripping followed by endothelial keratoplasty. Betamethasone 3.5 mg was subconjunctivally injected in groups control and D1 postoperatively, whereas rhesus monkeys in group D2 received topical 0.1% tacrolimus and topical steroids. All groups were evaluated by slit lamp, anterior segment optical coherence tomography, and laser scanning confocal microscopy for at least 9 months.

Results: Twenty-four monkeys met the inclusion criteria. Nine months after the DSAEK surgery, most corneas were transparent. Graft rejection was observed in 25% and 28.57% of the cases in group D1 and group D2 (p > 0.05), respectively. Corneal endothelium densities in DSAEK groups were 2,715.83 ± 516.20/mm2 (D1) and 2,220.00 ± 565.13/mm2 (D2) (p > 0.05).

Conclusions: Xenogeneic corneal endothelial grafts can survive and function in rhesus monkey eyes for a prolonged period of time with subconjunctival steroid or topical tacrolimus and steroid treatment. Furthermore, topical drugs are more suitable for clinical use.

Keywords: Corneal xenotransplantation; Descemet’s stripping automated endothelial keratoplasty; Immunosuppressor; Nonhuman primate.

MeSH terms

  • Animals
  • Descemet Membrane*
  • Descemet Stripping Endothelial Keratoplasty* / methods
  • Endothelium, Corneal
  • Graft Survival
  • Heterografts
  • Humans
  • Immunosuppression Therapy
  • Macaca mulatta
  • Swine
  • Tacrolimus / pharmacology
  • Transplantation, Heterologous

Substances

  • Tacrolimus