Caffeic acid phenethyl ester attenuates nuclear factor‑κB‑mediated inflammatory responses in M�ller cells and protects against retinal ganglion cell death

Abstract

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 κ light-chain-enhancer of activated B cells (NF-κB) 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-α and chemokine C-C ligand-2, in CAPE-treated rats. The hypertrophy of astrocytes and Müller cells (gliosis) caused by ONC was also found to be attenuated by CAPE, accompanied by the inhibition of NF-κB signaling. Similarly, in vitro , CAPE suppressed the proliferation and migration of primary astrocytes induced by lipopolysaccharide, as well as the activation of NF-κB. These results suggest that CAPE protected against RGC and attenuated inflammatory responses in a rat model of ONC by suppressing NF-κB activation.

A Dietary Combination of Forskolin with Homotaurine, Spearmint and B Vitamins Protects Injured Retinal Ganglion Cells in a Rodent Model of Hypertensive Glaucoma

“…As shown here, IOP elevation due to MCE injection activates an inflammatory cascade triggered by glial cell activation as determined by upregulated levels of both Iba-1, a marker of activated microglia, and GFAP, a marker of Müller cell gliosis. Downstream to their activation, glial cells trigger NF-κB that enters the nucleus and leads to the transcription of inflammatory cytokines including IL-6 and TNF-α, in line with previous findings in a rat model of ONC [48]. In turn, TNF-α upregulation exacerbates the inflammatory processes by increasing NF-kB activation, thus generating a positive feed-back loop.…”

CAPE and Neuroprotection: A Review

“…These effects are mediated by the decreased expression of the inflammatory cytokines IL-8 and IL-6, inducible nitric oxide synthase, cycloooxygenase-2, tumor necrosis factor-α, and chemokine C-C ligand-2. The hypertrophy of astrocytes and Müller cells (gliosis) was modulated by CAPE through the inhibition of NF-κB signaling [ 41 ].…”

Protection of the Retinal Ganglion Cells: Intravitreal Injection of Resveratrol in Mouse Model of Ocular Hypertension

“…In this way, labeled cells were identified, counted, and pooled together, as described previously. [49][50][51][52] All data were quantified using ImageJ software v1.51 (National Institutes of Health, Bethesda, MD, USA) as previously described, [53][54][55] which automatically calculated the number of Brn-3a-positive cells per image and the density of Brn-3a cells/mm 2 of retina in the five groups.…”