Retinal Protection and Distribution of Curcumin in Vitro and in Vivo

Abstract

Diabetic retinopathy (DR), a secondary complication of diabetes, is a leading cause of irreversible blindness accounting for 5% of world blindness cases in working age. Oxidative stress and inflammation are considered causes of DR. Curcumin, a product with anti-oxidant and anti-inflammatory properties, is currently proposed as oral supplementation therapy for retinal degenerative diseases, including DR. In this study we predicted the pharmacodynamic profile of curcumin through an in silico approach. Furthermore, we tested the anti-oxidant and anti-inflammatory activity of curcumin on human retinal pigmented epithelial cells exposed to oxidative stress, human retinal endothelial and human retinal pericytes (HRPCs) cultured with high glucose. Because currently marketed curcumin nutraceutical products have not been so far evaluated for their ocular bioavailability; we assessed retinal distribution of curcumin, following oral administration, in rabbit eye. Curcumin (10 μM) decreased significantly (p < 0.01) ROS concentration and TNF-α release in retinal pigmented epithelial cells and retinal endothelial cells, respectively. The same curcumin concentration significantly (p < 0.01) protected retinal pericytes from high glucose damage as assessed by cell viability and LDH release. Among the tested formulations, only that containing a hydrophilic carrier provided therapeutic levels of curcumin in rabbit retina. In conclusion, our data suggest that curcumin, when properly formulated, may be of value in clinical practice to manage retinal diseases.

Ocular Formulation Based on Palmitoylethanolamide-Loaded Nanostructured Lipid Carriers: Technological and Pharmacological Profile

“…Rat eyes (n = 12 per group) were collected 10 days after STZ administration, and each retina was homogenized in 100 mL of digest solution as previously described [19]. The solution was supplemented with a cocktail of protease inhibitors (Complete Protease Inhibitor Cocktail, Roche, Basel, Switzerland) before use.…”

Curcumin prevents high glucose damage in retinal pigment epithelial cells through ERK1/2‐mediated activation of the Nrf2/HO‐1 pathway

“…ANOVA: analysis of variance; HO-1: heme oxygenase-1; MAPK: mitogen-activated protein kinase; MTT: 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide; RPE: retinal pigment epithelial; SEM: standard error of mean protects retinal cells, such as RPE, in vitro models that recapitulate oxidative stress and inflammation in the diabetic retina and that could be a cause of inner and outer BRB breakdown (Huang et al, 2016;Platania et al, 2018;Ved et al, 2017). In particular, curcumin decreased significantly ROS concentration, LDH levels, and TNF-α release in human RPE cells, human retinal endothelial cells, and human retinal pericytes challenged with oxidative stress or HG (Platania et al, 2018). In accordance with the above studies, the present work demonstrated that curcumin provides protection against HG-induced damage in human RPE cells through the activation of Nrf2/HO-1 signaling that involves the modulation of the ERK pathway suggesting that curcumin may have therapeutic value in the treatment of DR. ORCID Velia D'Agata http://orcid.org/0000-0003-1114-8265 Salvatore Giunta http://orcid.org/0000-0002-8095-8678…”

Curcumin as a Therapeutic Option in Retinal Diseases

“…Regarding HERCs cells, treatment with 10 µM curcumin reverted the effect of 40 mM glucose leading to a significant decrease (p < 0.01) of tumor necrosis factor (TNF), similar to control cells, and on HRPCs cells the use of 10 µM curcumin prevented cell death caused by 40 mM glucose. On the in vivo test, different commercial available products containing curcumin were assessed, namely, curcumin formulation with a polyvinylpyrrolidone-hydrophilic carrier, curcumin-phosphatidylcholine complex and curcumin + piperine, after the intake at different times, the animals were sacrificed and the retinae were analyzed by HPLC-MS/MS showing that just the formulation with polyvinylpyrrolidone-hydrophilic carrier was able to reach the retina with a t MAX of 6 h after oral administration [30].…”