Curcumin protects retinal cells from light-and oxidant stress-induced cell death.
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 anti-inflammatory and antioxidative properties, in a 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-kappaB activation and down-regulation of cellular inflammatory genes. When tested on retina-derived cell lines (661W and ARPE-19), pretreatment 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-kappaB, 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.
Mandal
Md Nawajes A
MN
Department of Ophthalmology, University of Oklahoma Health Sciences Center, Oklahoma City, 73104, USA. mmandal@ouhsc.edu
Patlolla
Jagan M R
JM
Zheng
Lixin
L
Agbaga
Martin-Paul
MP
Tran
Julie-Thu A
JT
Wicker
Lea
L
Kasus-Jacobi
Anne
A
Elliott
Michael H
MH
Rao
Chinthalapally V
CV
Anderson
Robert E
RE
D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D002478:Cells, Cultured; D003474:Curcumin / Q000008:administration & dosage* / Q000494:pharmacology; D019610:Cytoprotection / Q000502:physiology; D019587:Dietary Supplements; D004195:Disease Models, Animal; D004596:Electroretinography; D020869:Gene Expression Profiling; D006801:Humans; D008027:Light / Q000009:adverse effects; D008268:Macular Degeneration / Q000188:drug therapy* / Q000201:enzymology / Q000209:etiology / Q000473:pathology; D051379:Mice; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D018384:Oxidative Stress / Q000502:physiology; D008517:Phytotherapy; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D017949:Retinal Cone Photoreceptor Cells / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D015533:Transcriptional Activation / Q000187:drug effects
D016328:NF-kappa B; D003474:Curcumin