Leukotriene B4 receptors as therapeutic targets for ophthalmic diseases.

Leukotriene B4 (LTB4) is an inflammatory lipid mediator produced from arachidonic acid by multiple reactions catalyzed by two enzymes 5-lipoxygenase (5-LOX) and LTA4 hydrolase (LTA4H). The two receptors for LTB4 have been identified: a high-affinity receptor, BLT1, and a low-affinity receptor, BLT2. Our group identified 12(S)-hydroxy-5Z,8E,10E-heptadecatrienoic acid (12-HHT) as a high-affinity BLT2 ligand. Numerous studies have revealed critical roles for LTB4 and its receptors in various systemic diseases. Recently, we also reported the roles of LTB4, BLT1 and BLT2 in the murine ophthalmic disease models of mice including cornea wound, allergic conjunctivitis, and age-related macular degeneration. Moreover, other groups revealed the evidence of the ocular function of LTB4. In the present review, we introduce the roles of LTB4 and its receptors both in ophthalmic diseases and systemic inflammatory diseases. LTB4 and its receptors are putative novel therapeutic targets for systemic and ophthalmic diseases.