Caffeic acid phenethyl ester attenuates nuclear factor-κB-mediated inflammatory responses in Muller cells and protects against retinal ganglion cell death

Glaucoma is characterized by the death of retinal ganglion cells (RGCs) and visual field defects, and is a leading cause of blindness worldwide. Caffeic acid phenethyl ester (CAPE), a natural polyphenolic found in propolis from honeybee hives, can inhibit the activation of nuclear factor kappa light-chain-enhancer of activated B cells (NF-kappa B) and has therapeutic potential in inflammatory disease. The present study used a rat model of optic nerve crush (ONC) injury to investigate the effect of CAPE on glaucoma. The death of RGCs at day 14 was significantly reduced in CAPE-treated animals compared with the non-treated group according to Brn3a and TUNEL staining. In addition, CAPE decreased the severity of inflammation in the retina, reflected by the decreased expression of inflammatory cytokines, including interleukin (IL)-8, IL-6, inducible nitric oxide synthase, cycloooxygenase-2, tumor necrosis factor-alpha and chemokine C-C ligand-2, in CAPE-treated rats. The hypertrophy of astrocytes and Muller cells (gliosis) caused by ONC was also found to be attenuated by CAPE, accompanied by the inhibition of NF-kappa B signaling. Similarly, in vitro, CAPE suppressed the proliferation and migration of primary astrocytes induced by lipopolysaccharide, as well as the activation of NF-kappa B. These results suggest that CAPE protected against RGC and attenuated inflammatory responses in a rat model of ONC by suppressing NF-kappa B activation.