Lipoxin A4 (LXA4) as a Potential Drug for Diabetic Retinopathy

The purpose of this review is to propose that lipoxin A4 (LXA4), derived from arachidonic acid (AA), a potent anti-inflammatory, cytoprotective, and wound healing agent, may be useful to prevent and manage diabetic retinopathy (DR). LXA4 suppresses inappropriate angiogenesis and the production of pro-inflammatory prostaglandin E2 (PGE2), leukotrienes (LTs), 12-HETE (12-hydroxyeicosatetraenoic acid), derived from AA by the action of 12-lioxygenase (12-LOX)) interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α), as well as the expression of NF-κB, inducible NO (nitric oxide) synthase (iNOS), cyclooxygenase-2 (COX-2), intracellular adhesion molecule-1 (ICAM-1), and vascular endothelial growth factor (VEGF)-factors that play a role in DR. Thus, the intravitreal injection of LXA4 may form a new approach to the treatment of DR and other similar conditions such as AMD (age-associated macular degeneration) and SARS-CoV-2-associated hyperinflammatory immune response in the retina. The data for this review are derived from our previous work conducted in individuals with DR and from various publications on LXA4, inflammation, and DR.