Abstract
Purpose: :
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 protective role of Caffeic Acid Phenethyl Ester (CAPE), an anti-oxidative and anti-inflammatory compound in oxidant (H2O2) induced mouse retina-derived cell lines 661W and light-induced retinal degeneration of albino rats.
Methods: :
The 661W cells were pre-treated with (1.0- 20.0 uM) CAPE for 3h and then stressed with 1 mM H2O2 for 6 h. Cell death was determined by lactate dehydrogenase (LDH) release assay. In albino Sprague Dawley rats, CAPE was administered intraperitoneally 0.5h before light-damage @ 2,700 lux for 6h or fed the AIN-96A diet supplemented with 0.01% CAPE for 15 days before light exposure. Retinal structure and function were determined after 7 days and tissue harvested for biochemical analyses immediately after exposure. In another set-up, rats were fed either AIN-96A diet or CAPE-supplemented AIN-96A diet and raised in either at 10-50 lux cyclic dim light or 400 lux cyclic bright light. Retinal structure and function were determined after 3 months without any further light treatment.
Results: :
H2O2 caused 27% cell death in 661W cells and pre-treatment with CAPE reduced the cell death in a dose dependent manner. CAPE treatment induces expression of HO1 (30-fold) gene and protein, and reduced the expression of iNos (7-fold). Systemic delivery of CAPE 0.5h before light-damage had slight protection. Feeding with CAPE-supplemented diet for 15 days did not show significant protection from light-damage, but the expression of c-fos, Fosl, and Lox5 genes were significantly reduced. Interestingly, the ERG responses of the CAPE-fed-unexposed retinas were significantly higher than the control-diet-fed-unexposed retina. This was further verified by feeding rats for 3 months and ERG responses were indeed significantly higher in the CAPE-fed-retinas.
Conclusions: :
CAPE can induce expression of HO1 gene, one of the major players in the cellular oxidative defense system in retinal cells, and reduce the expression of pro-apoptotic and lipoxygenase genes in light-damaged retinas. Long-term feeding restored retinal function better in albino rats. CAPE could be a potential candidate to be supplemented in diet for preservation of retinal function from day to day oxidative stress.
Keywords: oxidation/oxidative or free radical damage • retinal degenerations: cell biology • neuroprotection