curcumin and Retinal-Degeneration

Defective autophagy in the retinal pigment epithelium (RPE) is involved in retinal degeneration, mostly in the course of age-related macular degeneration (AMD), which is an increasingly prevalent retinal disorder, eventually leading to blindness. However, most autophagy activators own serious adverse effects when administered systemically. Curcumin is a phytochemical, which induces autophagy with a wide dose-response curve, which brings minimal side effects. Recent studies indicating defective autophagy in AMD were analyzed. Accordingly, in this perspective, we discuss and provide some evidence about the protective effects of curcumin in preventing RPE cell damage induced by the autophagy inhibitor 3-methyladenine (3-MA). Cells from human RPE were administered the autophagy inhibitor 3-MA. The cell damage induced by 3-MA was assessed at light microscopy by hematoxylin & eosin, Fluoro Jade-B, and ZO1 immunohistochemistry along with electron microscopy. The autophagy inhibitor 3-MA produces cell loss and cell degeneration of RPE cells. These effects are counteracted dose-dependently by curcumin. In line with the hypothesis that the autophagy machinery is key in sustaining the integrity of the RPE, here we provide evidence that the powerful autophagy inhibitor 3-MA produces dose-dependently cell loss and cell degeneration in cultured RPE cells, while inhibiting autophagy as shown by LC3-II/LC3-I ratio and gold-standard assessment of autophagy through LC3-positive autophagy vacuoles. These effects are prevented dose-dependently by curcumin, which activates autophagy. These data shed the perspective of validating the role of phytochemicals as safe autophagy activators to treat AMD.

Topics: Autophagy; Curcumin; Humans; Macular Degeneration; Oxidative Stress; Retinal Degeneration; Retinal Pigment Epithelium

Retinal degeneration is the major and principal cause behind many incurable blindness diseases. Several studies indicated the neuroprotective effect of Curcuma longa in eye pathologies, specifically retinopathy. However, the molecular mechanism behind its effect has not been completely elucidated. Using an

Topics: Antioxidants; Curcuma; Curcumin; Neuroprotective Agents; Plant Extracts; Retinal Degeneration; Sumoylation

Retinitis pigmentosa (RP) is characterized by degeneration of photoreceptors, and there are currently no effective treatments for this disease. However, curcumin has shown neuroprotectant efficacy in a RP rat and swine model, and thus, may have neuroprotective effects in this disease.. Immunofluorescence staining, electroretinogram recordings, and behavioral tests were used to analyze the effects of curcumin and the underlying mechanism in retinal degeneration 1 (rd1) mice.. The number of apoptotic cells in the retina of rd1 mice at postnatal day 14 significantly decreased with curcumin treatment and visual function was improved. The activation of microglia and secretion of chemokines and matrix metalloproteinases in the retina were inhibited by curcumin. These effects were also observed in a co-culture of BV2 microglial cells and retina-derived 661W cells.. Curcumin delayed retinal degeneration by suppressing microglia activation in the retina of rd1 mice. Thus, it may be an effective treatment for neurodegenerative disorders such as RP.

Topics: Animals; Apoptosis; Cell Movement; Cell Proliferation; Chemokines; Coculture Techniques; Curcumin; Electroretinography; Hydrogen Peroxide; Lipopolysaccharides; Matrix Metalloproteinases; Mice; Mice, Inbred C57BL; Microglia; Microscopy, Fluorescence; Neuroprotective Agents; Photoreceptor Cells, Vertebrate; Retina; Retinal Degeneration; Tissue Inhibitor of Metalloproteinase-1; Vascular Cell Adhesion Molecule-1; Visual Acuity

The P23H mutation in the rhodopsin gene causes rhodopsin misfolding, altered trafficking and formation of insoluble aggregates leading to photoreceptor degeneration and autosomal dominant retinitis pigmentosa (RP). There are no effective therapies to treat this condition. Compounds that enhance dissociation of protein aggregates may be of value in developing new treatments for such diseases. Anti-protein aggregating activity of curcumin has been reported earlier. In this study we present that treatment of COS-7 cells expressing mutant rhodopsin with curcumin results in dissociation of mutant protein aggregates and decreases endoplasmic reticulum stress. Furthermore we demonstrate that administration of curcumin to P23H-rhodopsin transgenic rats improves retinal morphology, physiology, gene expression and localization of rhodopsin. Our findings indicate that supplementation of curcumin improves retinal structure and function in P23H-rhodopsin transgenic rats. This data also suggest that curcumin may serve as a potential therapeutic agent in treating RP due to the P23H rhodopsin mutation and perhaps other degenerative diseases caused by protein trafficking defects.

Topics: Animals; Chlorocebus aethiops; COS Cells; Curcumin; Immunohistochemistry; Mutagenesis, Site-Directed; Polymerase Chain Reaction; Rats; Rats, Sprague-Dawley; Rats, Transgenic; Retina; Retinal Degeneration; Rhodopsin

Chronic exposure to oxidative stress causes damage to retinal pigment epithelial cells which may lead to the development of age-related macular degeneration, the major cause of vision loss in humans. Anti-oxidants provide a natural defense against retinal cell damage. The present study was designed to evaluate the potential anti-oxidant activity and protective effect of two diarylheptanoids isolated from a medicinal herb Curcuma comosa; 7-(3,4 dihydroxyphenyl)-5-hydroxy-1-phenyl-(1E)-1-heptene (compound A), and 1,7-diphenyl-4(E),6(E)-heptadien-3-ol (compound B) against oxidative stress (H(2)O(2))-induced human retinal pigment epithelial (APRE-19) cell death. The 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay indicated that the anti-oxidant activity (IC(50)) of compound A was similar to that of vitamin C. Pre-treatment of ARPE-19 cells with 20 μM compound A for 4h afforded greater protection against the insult from 500 μM H(2)O(2), compared to a similar protection period for compound B. Compound A lowered H(2)O(2)-induced lipid peroxidation, malondialdehyde formation and intracellular reactive oxygen species. Furthermore, compound A ameliorated the H(2)O(2)-induced decrease in anti-oxidant enzyme activities and subsequent apoptotic cell death in ARPE-19 cells in a dose and time-dependent manner. These results suggest that compound A protects ARPE-19 cells against oxidative stress, in part, by enhancing several anti-oxidant defense mechanisms. Therefore, compound A may have therapeutic potential for diseases associated with oxidative stress, particularly degenerative retinal diseases.

Topics: Antioxidants; Apoptosis; Catalase; Cell Line; Cell Survival; Curcuma; Diarylheptanoids; Dietary Supplements; Free Radical Scavengers; Glutathione Peroxidase; Heptanes; Heptanol; Humans; Hydrogen Peroxide; Lipid Peroxidation; Malondialdehyde; Oxidants; Oxidative Stress; Reactive Oxygen Species; Retinal Degeneration; Retinal Pigment Epithelium; Superoxide Dismutase