Investigation of DHA-Induced Regulation of Redox Homeostasis in Retinal Pigment Epithelium Cells through the Combination of Metabolic Imaging and Molecular Biology

Antioxidants

Cassandra Serantoni¹  Giuseppe Maulucci¹  Marco De Spirito¹  Giada Bianchetti¹  Alessio Abeltino¹  Shlomo Sasson²  Maria Elisabetta Clementi³  Beatrice Sampaolese³ 

[1]Department of Neuroscience, Biophysics Sections, Università Cattolica del Sacro Cuore, Largo Francesco Vito, 1, 00168 Rome, Italy

[2]Faculty of Medicine, Institute for Drug Research, The Hebrew University, Jerusalem 911210, Israel

[3]Institute of Chemical Sciences and Technologies “Giulio Natta” (SCITEC)—CNR, Largo Francesco Vito, 1, 00168 Rome, Italy

关键词: diabetic retinopathy;    oxidative stress;    docosahexaenoic acid (DHA);    blood-retinal barrier;    retinal diseases;    therapeutic approach;   

DOI  :  10.3390/antiox11061072

来源: DOAJ

【 摘 要 】

Diabetes-induced oxidative stress leads to the onset of vascular complications, which are major causes of disability and death in diabetic patients. Among these, diabetic retinopathy (DR) often arises from functional alterations of the blood-retinal barrier (BRB) due to damaging oxidative stress reactions in lipids, proteins, and DNA. This study aimed to investigate the impact of the ω3-polyunsaturated docosahexaenoic acid (DHA) on the regulation of redox homeostasis in the human retinal pigment epithelial (RPE) cell line (ARPE-19) under hyperglycemic-like conditions. The present results show that the treatment with DHA under high-glucose conditions activated erythroid 2-related factor Nrf2, which orchestrates the activation of cellular antioxidant pathways and ultimately inhibits apoptosis. This process was accompanied by a marked increase in the expression of NADH (Nicotinamide Adenine Dinucleotide plus Hydrogen) Quinone Oxidoreductase 1 (Nqo1), which is correlated with a contextual modulation and intracellular re-organization of the NAD+/NADH redox balance. This investigation of the mechanisms underlying the impairment induced by high levels of glucose on redox homeostasis of the BRB and the subsequent recovery provided by DHA provides both a powerful indicator for the detection of RPE cell impairment as well as a potential metabolic therapeutic target for the early intervention in its treatment.

【 授权许可】

Unknown