CAPE protects retinal cells from oxidative stress-mediated cell death and preserves retinal function of dim light stressed albino rats when supplemented in diet

PURPOSE: Caffeic acid phenethyl ester (CAPE), an active component of honeybee propolis, has a wide range of beneficial properties, including anti-oxidant and anti-inflammatory properties. The role of oxidative stress and inflammation is being established as major fundamental components in different forms of retinal degenerative diseases. The purpose of this study was to test the role of CAPE in mouse retina-derived cell lines 661W by using H₂O₂, and in albino Sprague Dawley (SD) rats’retina by using chronic dim or bright light-induced retinal degeneration system.
METHODS: In vitro study, the 661W cells were pre-treated with (1.0– 20.0 uM) CAPE for 3h, then stressed with 1 mM H₂O₂for 6 h. Cell death was determined by lactate dehydrogenase (LDH) release assay. In vivo study, SD rats, raised either under dim (10-50 lux) cyclic light or bright (400 lux) cyclic light, were fed with either AIN-96A diet (control) or AIN-96A diet supplemented with CAPE (0.01%) for 2-8 weeks. In both vitro and vivo, the gene and protein expression were analyzed. Further in vitro, retinal structure and function were determined by histology and ERG, and the fatty acid was analyzed by Gas-chromotograpgy (GC).
RESULTS: In vitro, pre-treatment of CAPE reduced the cell death in a dose dependent manner, and induced expression of Hemoxygenase-1, but reduced the protein expression of IKBa. In vivo, under dim light, increased expression of Ho1 and Icam1 and decreased expression of Fosl and Lox12 genes were found in CAPE-fed retinas, accompanied with decreased translocation of NFKb protein to the nucleus. In addition, the molar ratio of poly-unsaturated fatty acids (20:2n6, 20:4n6, 22:4n6, 22:6n3 (DHA), 24:6n3) decreased significantly in CAPE-fed retinas under dim light. Further, the ERG of the CAPE-fed retinas was significantly higher than the control-diet-fed retina in dim light either for 2 weeks or 8 weeks. But under bright light, few changes in the ERG, gene/protein expression and fatty acid composition were observed.
CONCLUSIONS: CAPE can activate anti-oxidative defense system in vitro and modulate lipid profile and preserve retinal function in vivo. It can be a potential candidate for supplementation in diet for preservation of retinal function from day to day oxidative stress.