Xiuyun Li1, Aijun Deng1, Jianwei Liu1, Weikai Hou2. 1. Department of Ophthalmology, Affiliated Hospital of Weifang Medical University Weifang, Shandong Province, China. 2. Department of Endocrinology, Qilu Hospital of Shandong University Jinan 250012, Shandong Province, China.
Abstract
OBJECTIVE: Diabetic retinopathy (DR) is one severe complication of diabetes, and involves reactive oxygen species (ROS) produced under oxidative stress (OS) conditions. Keap1-Nrf2-ARE is one important endogenous anti-OS signal pathway. This study generated a type 2 DR rat model, on which expression of Nrf2/ARE pathway related proteins were measured to investigate functional role and mechanism of Keap1-Nrf2-ARE signal pathway in DR. PATIENTS AND METHODS: Using DR model rats, blood samples were collected for measuring FBG, TC, TG, HDL-C, and LDL-C for evaluating blood glucose and lipid. Retinas were collected for measuring ROS content using DCFH-DA staining, and caspase-3 activity was measured by colorimetry. Cell apoptosis was measured by flow cytometry. Keap1 and Nrf2 proteins were quantified by Western blot. Aqueous humor was collected for measuring MDA, SOD, GSH-Px, and T-AOC. RESULTS: Model rats had significantly elevated blood FBG, TG, TC, and LDL-C, plus decreased HDL-C. Model rats also had higher retinal ROS content, enhanced caspase-3 activity, and potentiated apoptosis. Compared to the control group, model rats had elevated MDA and lower activity of SOD, GSH-Px, and T-AOC in aqueous humor, plus lower Keap1 and higher Nrf2 expression in retina. CONCLUSION: DR rats showed significantly elevated retinal apoptosis, with prominent OS. Under diabetic conditions, activation of Keap1-Nrf2-ARE pathway may play a role in alleviating OS damage and protecting retina. IJCEP
OBJECTIVE:Diabetic retinopathy (DR) is one severe complication of diabetes, and involves reactive oxygen species (ROS) produced under oxidative stress (OS) conditions. Keap1-Nrf2-ARE is one important endogenous anti-OS signal pathway. This study generated a type 2 DRrat model, on which expression of Nrf2/ARE pathway related proteins were measured to investigate functional role and mechanism of Keap1-Nrf2-ARE signal pathway in DR. PATIENTS AND METHODS: Using DR model rats, blood samples were collected for measuring FBG, TC, TG, HDL-C, and LDL-C for evaluating blood glucose and lipid. Retinas were collected for measuring ROS content using DCFH-DA staining, and caspase-3 activity was measured by colorimetry. Cell apoptosis was measured by flow cytometry. Keap1 and Nrf2 proteins were quantified by Western blot. Aqueous humor was collected for measuring MDA, SOD, GSH-Px, and T-AOC. RESULTS: Model rats had significantly elevated blood FBG, TG, TC, and LDL-C, plus decreased HDL-C. Model rats also had higher retinal ROS content, enhanced caspase-3 activity, and potentiated apoptosis. Compared to the control group, model rats had elevated MDA and lower activity of SOD, GSH-Px, and T-AOC in aqueous humor, plus lower Keap1 and higher Nrf2 expression in retina. CONCLUSION:DRrats showed significantly elevated retinal apoptosis, with prominent OS. Under diabetic conditions, activation of Keap1-Nrf2-ARE pathway may play a role in alleviating OS damage and protecting retina. IJCEP
Authors: Silvia M Sanz-González; José J García-Medina; Vicente Zanón-Moreno; María I López-Gálvez; David Galarreta-Mira; Lilianne Duarte; Mar Valero-Velló; Ana I Ramírez; J Fernando Arévalo; María D Pinazo-Durán Journal: Antioxidants (Basel) Date: 2020-11-09