Study on the mechanism of 20-hydroxyeicosatetraenoic acid in retinal ischemia–reperfusion injury

Abstract

Purpose: To explore the effect of 20-hydroxyeicosatetraenoic acid (20-HETE) on retinal ischemia–reperfusion injury (RIRI) and the protective effect of N‐hydroxy‐N’‐(4‐n‐butyl‐2‐methylphenyl)formamidine (HET0016) on RIRI. Methods: Male Sprague–Dawley rats were randomly divided into the normal control group, experimental model group (RIRI group), experimental solvent group (RIRI + solvent group), and experimental treatment group (RIRI + HET0016 group). Results: The levels of 20-HETE, tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β) in the retina of rats at 24 h after reperfusion were measured by enzyme-linked immunosorbent assay. Hematoxylin–eosin staining was used to observe the retinal morphological and thickness changes at 24 h, 48 h, and 7 days after reperfusion. The number and localized expression of matrix metalloproteinase-9–positive cells in the retina of the rats at 24 h after reperfusion and the activation and localized expression of retinal microglia at 48 h after reperfusion were measured using an immunohistochemical method. The nuclear metastasis of nuclear factor kappa-B (NF-κB, p65) cells at 24 h after reperfusion was observed using an immunofluorescence method. Conclusion: Overall, 20-HETE might activate microglia to aggravate RIRI by the NF-κB pathway, but HET0016 has significant protective effects for the retina.