Hypoxia and the Prolyl Hydroxylase Inhibitor FG-4592 Protect Corneal Endothelial Cells From Mechanical and Perioperative Surgical Stress

Cornea. 2018 Apr;37(4):501-507. doi: 10.1097/ICO.0000000000001430.

Abstract

Purpose: To determine whether hypoxia preconditioning can protect corneal endothelial cells from mechanical stress and perioperative procedures mimicking Descemet stripping automated endothelial keratoplasty (DSAEK).

Methods: Preconditioning was delivered by 2 hours of 0.5% oxygen incubation in a hypoxia chamber or by exposure to the prolyl hydroxylase inhibitor FG-4592, which prevents hypoxia-inducible factor-1 alpha degradation. Damage to whole corneas was produced by brief sonication. To mimic use with DSAEK, FG-4592-preconditioned and control donor corneas were dissected with a microkeratome, and the posterior donor button was pulled through a transplant insertion device (Busin glide). The area of endothelial damage was determined by trypan blue staining.

Results: In all cases, hypoxia preconditioning or incubation with FG-4592 protected corneal endothelial cells from death by mechanical stress. Hypoxia-preconditioned human and rabbit corneas showed 19% and 29% less cell loss, respectively, relative to controls, which were both significant at P < 0.05. FG-4592 preconditioning reduced endothelial cell loss associated with preparation and insertion of DSAEK grafts by 23% relative to the control (P < 0.01).

Conclusions: These results support the hypothesis that preconditioning by hypoxia or exposure to FG-4592 improves corneal endothelial cell survival and may also provide protection during surgical trauma.

MeSH terms

  • Animals
  • Cell Line
  • Cell Survival
  • Corneal Endothelial Cell Loss / prevention & control*
  • Cytoprotection
  • Descemet Stripping Endothelial Keratoplasty
  • Endothelium, Corneal / drug effects*
  • Endothelium, Corneal / pathology
  • Glycine / analogs & derivatives*
  • Glycine / pharmacology
  • Humans
  • Hypoxia / prevention & control*
  • Ischemic Preconditioning*
  • Isoquinolines / pharmacology*
  • Oxygen / pharmacology*
  • Perioperative Care
  • Pilot Projects
  • Prolyl-Hydroxylase Inhibitors / pharmacology*
  • Rabbits
  • Stress, Mechanical

Substances

  • FG-4592
  • Isoquinolines
  • Prolyl-Hydroxylase Inhibitors
  • Oxygen
  • Glycine