Curcumin protects retinal cells from light-and oxidant stress-induced cell death

Abstract

Age-related macular degeneration (AMD) is a complex disease that has potential involvement of inflammatory and oxidative stress-related pathways in its pathogenesis. In search of effective therapeutic agents, we tested curcumin, a naturally-occurring compound with known antiinflammatory and anti-oxidative properties, in rat model of light induced retinal degeneration (LIRD) and in retina derived cell lines. We hypothesized that any compound effective against LIRD, which involves significant oxidative stress and inflammation, would be a candidate for further characterization for its potential application in AMD.We observed significant retinal neuroprotection in rats fed diets supplemented with curcumin (0.2% in diet) for 2 weeks. The mechanism of retinal protection from LIRD by curcumin involves inhibition of NF-κB activation and down-regulation of cellular inflammatory genes. When tested on retinaderived cell lines (661W and ARPE-19), pre-treatment of curcumin protected these cells from H 2 O 2 -induced cell death by up-regulating cellular protective enzymes, such as HO-1, thioredoxin.Since, curcumin with its pleiotropic activities can modulate the expression and activation of many cellular regulatory proteins such as NF-κB, AKT, NRF2 and growth factors, which in turn inhibit cellular inflammatory responses and protect cells; we speculate that curcumin would be an effective nutraceutical compound for preventive and augmentative therapy of AMD.

Inhibition of de novo ceramide biosynthesis by FTY720 protects rat retina from light-induced degeneration

“…Flash ERGs were recorded with the Diagnosys Espion E2 ERG System (Diagnosys, LLC; Lowell, MA) as described in previous publications ( 15,16 ). For the assessment of rod photoreceptor function (scotopic ERG), four strobe fl ash stimuli were presented at fl ash intensities of Ϫ 2.3, Ϫ 1.3, 0.7, and 2.7 log cd.s/m 2 .…”

“…After ERG recordings, rats were euthanized by carbon dioxide asphyxiation for light microscopic evaluation of retinal structure following previously published methods ( 15,16 ). In brief, eyes were harvested and marked with a tattoo dye at the 12 o'clock position on the limbus and fi xed.…”

“…Quantitative PCR and melt-curve analyses were performed using iQ SYBR Green Supermix (Bio-Rad; Hercules, CA) and an iCycler machine. Relative quantities of expression of the genes of interest in different samples were calculated by the comparative Ct (threshold cycle) value method ( 16,(48)(49)(50).…”

“…in complete loss of photoreceptor cells from the central superior retina within 7 days ( 15,16,20,58,59 ). We measured retinal free ceramide levels at different time points after light damage prior to (0 h, 3 h, and 6 h after exposure) and after the onset of apoptosis (12 h, 24 h, 48 h).…”

NRF2 and Age-Dependent RPE Degeneration

“…colleagues first reported that sulforaphane could prevent RPE cell death caused by treatments with menadione, t-butyl hydroperoxide, 4-hydroxynonenal and peroxynitrite (Gao et al, 2001). Since then numerous other studies reported the protective effects of a wide range of structurally-different NRF2 inducers including isothiocyanates (sulforaphane) (Gao & Talalay, 2004), polyphenols (curcumin, resveratrol and flavonoids) (Alex et al, 2010;Johnson et al, 2009;Mandal et al, 2009), 1,2,dithiole-3-thiones (oltipraz) (Nelson et al, 2002), zinc (Ha et al, 2006) or triterpenoids (Pitha-Rowe et al, 2009). Many of them are naturally occurring compounds present in fruits and vegetables, making them ideal for dietary supplementation.…”