Curcumin Inhibits Neuronal and Vascular Degeneration in Retina after Ischemia and Reperfusion Injury

Abstract

BackgroundNeuron loss, glial activation and vascular degeneration are common sequelae of ischemia-reperfusion (I/R) injury in ocular diseases. The present study was conducted to explore the ability of curcumin to inhibit retinal I/R injury, and to investigate underlying mechanisms of the drug effects.Methodology/Principal FindingsDifferent dosages of curcumin were administered. I/R injury was induced by elevating the intraocular pressure for 60 min followed by reperfusion. Cell bodies, brn3a stained cells and TUNEL positive apoptotic cells in the ganglion cell layer (GCL) were quantitated, and the number of degenerate capillaries was assessed. The activation of glial cells was measured by the expression level of GFAP. Signaling pathways including IKK-IκBα, JAK-STAT1/3, ERK/MAPK and the expression levels of β-tubulin III and MCP-1 were measured by western blot analysis. Pre-treatment using 0.01%–0.25% curcumin in diets significantly inhibited I/R-induced cell loss in GCL. 0.05% curcumin pre-treatment inhibited I/R-induced degeneration of retinal capillaries, TUNEL-positive apoptotic cell death in the GCL, brn3a stained cell loss, the I/R-induced up-regulation of MCP-1, IKKα, p-IκBα and p-STAT3 (Tyr), and down-regulation of β-tubulin III. This dose showed no effect on injury-induced GFAP overexpression. Moreover, 0.05% curcumin administered 2 days after the injury also showed a vaso-protective effect.Conclusions/SignificanceCurcumin protects retinal neurons and microvessels against I/R injury. The beneficial effects of curcumin on neurovascular degeneration may occur through its inhibitory effects on injury-induced activation of NF-κB and STAT3, and on over-expression of MCP-1. Curcumin may therefore serve as a promising candidate for retinal ischemic diseases.

Anti-Inflammatory Effects of Lutein in Retinal Ischemic/Hypoxic Injury: In Vivo and In Vitro Studies

“…In I/R retina, Müller cell gliosis and hypertrophy are complications that worsen the pathological conditions. Retinal Müller cells exhibit hypertrophic morphology and increased expression of GFAP in ocular diseases such as retinal I/R injury 57,58 and diabetic retinopathy. 59 In fact, a Müller cell is one of the primary sources of pro-inflammatory cytokine during injuries.…”

“…58,59,[67][68][69] We speculated that lutein inhibits IL1b and Cox-2 expression through the reduction of NF-jB nuclear translocation in rMC-1 cells. Indeed, our findings demonstrated that expression of the active form of NF-jB, P-NF-jB, was up-regulated in nuclear extract after CoCl 2 -induced hypoxia, indicating the activation of NF-jB signaling similar to that in human skin keratinocytes (HaCaT cells).…”

Adaptive Cellular Stress Pathways as Therapeutic Targets of Dietary Phytochemicals: Focus on the Nervous System

“…Curcumin protected cultured neuronal cells against death induced by iodoacetate, an inhibitor of glycolysis (Reyes-Fermín et al, 2012). Curcumin treatment also reduced neuronal and microvessel degeneration in the retina in a rat model of ischemiareperfusion injury (Wang et al, 2011c). Catechins protected cultured neurons against death induced by the mitochondrial toxin 3-nitropropionic acid (3NP) (Nath et al, 2012).…”

Curcumin inhibits autophagy and apoptosis in hypoxia/reoxygenation-induced myocytes

“…Previous studies have demonstrated that curcumin attenuates I/R injury in various organs in vivo and in vitro, including the intestines, retina, liver and renal system, through anti-oxidative stress and anti-apoptotic mechanisms (20)(21)(22)(23) through the attenuation of oxidative stress and mitochondrial dysfunction. However, the beneficial effects of curcumin on the extent of apoptosis and autophagy in myocardial I/R, and their potential mechanisms, remain to be elucidated.…”