curcumin and Vitreoretinopathy--Proliferative

To review the role of curcumin in retinal diseases, COVID era, modification of the molecule to improve bioavailability and its future scope.. PubMed and MEDLINE searches were pertaining to curcumin, properties of curcumin, curcumin in retinal diseases, curcumin in diabetic retinopathy, curcumin in age-related macular degeneration, curcumin in retinal and choroidal diseases, curcumin in retinitis pigmentosa, curcumin in retinal ischemia reperfusion injury, curcumin in proliferative vitreoretinopathy and curcumin in current COVID era.. In experimental models, curcumin showed its pleiotropic effects in retinal diseases like diabetic retinopathy by increasing anti-oxidant enzymes, upregulating HO-1, nrf2 and reducing or inhibiting inflammatory mediators, growth factors and by inhibiting proliferation and migration of retinal endothelial cells in a dose-dependent manner in HRPC, HREC and ARPE-19 cells. In age-related macular degeneration, curcumin acts by reducing ROS and inhibiting apoptosis inducing proteins and cellular inflammatory genes and upregulating HO-1, thioredoxin and NQO1. In retinitis pigmentosa, curcumin has been shown to delay structural defects of P23H gene in P23H-rhodopsin transgenic rats. In proliferative vitreoretinopathy, curcumin inhibited the action of EGF in a dose- and time-dependent manner. In retinal ischemia reperfusion injury, curcumin downregulates IL-17, IL-23, NF. Curcumin is an easily available spice used traditionally in Indian cooking. The benefits of curcumin are manifold, and large randomized controlled trials are required to study its effects not only in treating retinal diseases in humans but in their prevention too.

Topics: Animals; COVID-19; Curcumin; Diabetic Retinopathy; Endothelial Cells; Humans; Macular Degeneration; Rats; Reperfusion Injury; Retinal Diseases; Retinal Neoplasms; Retinitis Pigmentosa; Vitreoretinopathy, Proliferative

Curcumin, the major extraction of turmeric, has been widely used in many countries for centuries both as a spice and as a medicine. In the last decade, researchers have found the beneficial effects of curcumin on multiple disorders are due to its antioxidative, anti-inflammatory, and antiproliferative properties, as well as its novel function as an inhibitor of histone aectyltransferases. In this review, we summarize the recent progress made on studying the beneficial effects of curcumin on multiple retinal diseases, including diabetic retinopathy, glaucoma, and age-related macular degeneration. Recent clinical trials on the effectiveness of phosphatidylcholine formulated curcumin in treating eye diseases have also shown promising results, making curcumin a potent therapeutic drug candidate for inflammatory and degenerative retinal and eye diseases.

Topics: Animals; Anti-Inflammatory Agents; Clinical Trials as Topic; Curcuma; Curcumin; Diabetic Retinopathy; Disease Models, Animal; Glaucoma; Humans; Inflammation; Macular Degeneration; Retinal Diseases; Retinitis Pigmentosa; Retinoblastoma; Vitreoretinopathy, Proliferative

Topics: Animals; Curcumin; Electroretinography; Enzyme Inhibitors; Intravitreal Injections; Male; Rabbits; Retina; Tomography, Optical Coherence; Vitreoretinopathy, Proliferative; Vitreous Body

This study aimed to explore the inhibitory effect of biodegradable scleral plugs containing curcumin on rabbits with proliferative vitreoretinopathy (PVR).. The biodegradable scleral plugs containing curcumin were prepared by dissolving PLGA [poly(lactide-co-glycolide)] and curcumin. In total, 30 rabbits were divided into 2 groups: the model group received a vitreous injection of self-blood, and the treatment group received a vitreous injection of self-blood plus biodegradable scleral implants containing 1.5 mg of curcumin. On days 1, 3, 7, 14, 21, and 28 after the operation, clinical observations and PVR classifications were performed. Then, after vitreous samples were collected, different cytokines were detected using antibody chip technology.. The scleral plug was 5 mm in length and 1 mm in diameter. Clinical observation showed marked inflammation in the model group. The development grade of PVR in the treatment group was lower than that in the model group (p < 0.05). The outcome of antibody chip technology showed that the expression levels of IL-1α, IL-1β, IL-8, leptin, MMP-9, NCAM, and TNF-α in the treatment group at different time points were significantly lower than those in the model group (p < 0.05).. Curcumin might have great potential as a therapeutic agent for PVR by inhibiting various inflammatory factors.

Topics: Absorbable Implants; Animals; Anti-Inflammatory Agents, Non-Steroidal; Curcumin; Cytokines; Disease Models, Animal; Drug Delivery Systems; Rabbits; Sclera; Vitreoretinopathy, Proliferative

Proliferative vitreoretinopathy (PVR) is a common refractory eye disease that causes blindness and occurs after retinal detachment or retinal reattachment. Epidermal growth factor (EGF) has been shown to play an important role in the migration and proliferation of retinal pigment epithelium (RPE) cells, which promote PVR. Curcumin inhibits RPE cell proliferation, but it is not known whether it participates in the formation of PVR. Curcumin regulates the biological functions of EGF, which plays important roles in the development of PVR. This study aimed to evaluate the effect of curcumin on the regulation of EGF in PVR.. Rabbit RPE cells were cultured, and EGF expression was detected by immunocytochemistry. MTT assay was conducted to determine cell proliferation induced by different concentrations of EGF. Immunocytochemical staining was used to detect EGF expression after treatment with curcumin at varying concentrations. Real-time PCR (RT-PCR) and western blot analysis were used to detect the concentrations of EGF mRNA and protein after treatment with curcumin. After RPE cells and curcumin were injected into experimental rabbit eyes, the cornea, aqueous humor, lens, and vitreous opacity were observed and recorded simultaneously by indirect ophthalmoscopy, fundus color photography, and B-ultrasonography. The vitreous body was extracted, and the EGF content in the vitreous humor was measured by enzyme-linked immunosorbent assay (ELISA).. At each time point (24, 48, and 72 h), cell proliferation gradually increased with increasing EGF concentrations (0, 3, 6, and 9 ng/mL) in a dose-dependent manner. Cell proliferation between EGF concentrations of 9 and 12 ng/mL were no different, which suggested that 9 ng/mL EGF was the best concentration to use to stimulate RPE cell proliferation in vitro. Under all EGF concentrations (0, 3, 6, 9, and 12 ng/mL), RPE cell proliferation increased with time (from 24 to 72 h), suggesting a time-effect relationship. Curcumin downregulated EGF expression in RPE cells, which also indicated time-effect and dose-effect relationships. The best curcumin concentration for the inhibition of EGF expression was 15 µg/mL. RT-PCR and western blot analyses indicated that the EGF mRNA and expression of the protein in RPE cells treated with curcumin significantly decreased with time. Ocular examinations revealed that the vitreous opacity was lower and the proliferative membrane was thinner in the curcumin group compared with the control group. The PVR grade and the incidence of retinal detachment were significantly lower in the experimental group than in the control group. ELISA results showed that the EGF content in vitreous humor was higher in the control group than in the curcumin group. The curcumin and control groups were significantly different at each time point.. Curcumin inhibited RPE cell proliferation by downregulating EGF and thus effectively inhibited the initiation and development of PVR.

Topics: Animals; Cell Proliferation; Curcumin; Disease Models, Animal; Dose-Response Relationship, Drug; Epidermal Growth Factor; Rabbits; Retinal Pigment Epithelium; Vitreoretinopathy, Proliferative

Proliferative vitreoretinopathy (PVR) is a disease caused by dedifferentiation, translocation and proliferation of several types of local cells. These cells form fibrocellular membranes resulting in detachment of retinal and vision loss. PVR occurs in 8%-10% of patients undergoing primary retinal detachment (RD) surgery and becomes a major obstacle for successful RD repair. Retinal pigment epithelial (RPE) cells are among the major cells which consist of fibrocellular membranes. Reproliferation and Epithelial-mesenchymal transition (EMT) are the primary pathological alteration of RPE cells in PVR.. RPE cells were treated with curcumin at different concentrations for 24, 48 and 72 hours. The viable cells were detected by MTT assay. The apoptosis of RPE was stained by Multicaspase/7-AAD and detected using flow cytometry. Cell cycle analysis was quantified by PI staining. The mRNA levels were detected by real-time PCR. The protein levels were detected by western blot.. We found a compound curcumin significantly inhibited proliferation and EMT of RPE cells in vitro. Further study showed curcumin induced cell cycle arrest by activating G2 checkpoint through p53 pathway. Meanwhile, we found that curcumin suppressed the AKT, MAPK and TGF-β pathways in RPE cells which may also affect proliferation and EMT. Our research identified curcumin a potential novel agent for the PVR prevention and treatment. Curcumin induces cell cycle arrest by activating G2 checkpoint.. Our results in this study also provide the insights to broaden the application of curcumin in research and probably clinics.

Topics: Animals; Cell Line; Cell Proliferation; Curcumin; Epithelial Cells; Epithelial-Mesenchymal Transition; Humans; Mice; Retinal Pigment Epithelium; Signal Transduction; Vitreoretinopathy, Proliferative

Proliferative vitreoretinopathy (PVR) is characterized by the presence of epiretinal membrane (ERM), which exerts traction and detaches the retina. Epithelial to mesenchymal transition (EMT) of the retinal pigment epithelial (RPE) cells underlies ERM formation. Adjuvant therapies aimed at preventing recurrence of PVR after surgery mostly failed in clinical trials. This study was aimed to evaluate the anti-EMT properties of bio-active compounds epigallocatechin gallate (EGCG), curcumin and lycopene as inhibitors of EMT induced by transforming growth factor beta 1 (TGF-β1) in cultured ARPE-19 cells.. ARPE-19 cells were treated with TGF-β1 alone or co-treated with EGCG (1-50 μM), lycopene (1-10 μM) and curcumin (1-10 μM). The mRNA and protein expression of EMT markers, alpha-smooth muscle actin, vimentin, zonula occludens-1 and matrix metalloproteinase-2 (MMP-2), were assessed by reverse transcription polymerase chain reaction/quantitative polymerase chain reaction and immunofluorescence/enzyme linked immunosorbent assay. Activity of MMP-2 was assessed by zymography. Functional implications of EMT were assessed by proliferation assay (MTT assay) and migration assay (scratch assay). Western-blot for phosphorylated Smad-3 and total Smad-3 was done to delineate the mechanism.. EGCG and curcumin at 10 μM concentration reversed EMT, inhibited proliferation and migration through Smad-3 phosphorylation, when induced by TGF-β1 in ARPE-19 cells. Lycopene did not prevent EMT in ARPE-19 cells.. EGCG and curcumin are potent in preventing EMT induced by TGF-β1 in ARPE-19 cells and therefore, proposed as potential molecules for further pre-clinical evaluation in PVR management.

Topics: Catechin; Cell Movement; Cell Proliferation; Curcumin; Epithelial Cells; Epithelial-Mesenchymal Transition; Humans; Matrix Metalloproteinase 2; Phosphorylation; Retinal Pigment Epithelium; Smad3 Protein; Transforming Growth Factor beta1; Vitreoretinopathy, Proliferative