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

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

methodsPreconditioning 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.

resultsIn 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).

conclusionsThese 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.