title: Potential Role of Endoplasmic Reticulum Stress in Pathogenesis of Diabetic Retinopathy.
abstract: Diabetes mellitus is a metabolic disease that leads to several complications which include retinopathy. Multiple biochemical abnormalities have been proposed to explain the development of retinopathy, including oxidative stress. Although the existence of oxidative stress has been established in the retina from long standing diabetic animals, pathogenesis and progression of retinopathy remain unclear. In order to gain insight into the pathogenesis of diabetic retinopathy, we analyzed the levels of different oxidative stress biomarkers in the retina at early stages during the progress of streptozotocin-induced diabetes. No significant changes in glutathione content, expression of NADPH-oxidase, levels of lipid peroxidation, nor production of free radicals were observed in the retina up to 45 days of diabetes induction. Likewise, a transient decrease in aconitase activity, parallel to an increase in the superoxide dismutase activity was observed at 20 days of hyperglycemia, suggesting a high capacity of retina to maintain its redox homeostasis, at least at early stages of diabetes. Nonetheless, we found an early and time-dependent increase in the levels of oxidized proteins, which was not affected by the administration of the antioxidant quercetin. Also, positive immunoreactivity to the reticulum stress protein CHOP was found in glial Müller cells of diabetic rat retinas. These findings suggest the occurrence of endoplasmic reticulum stress as a primary event in retina pathogenesis in diabetes.
authors.affiliation: División de Neurociencias, Departamento de Neurodesarrollo y Fisiología, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Apdo. Postal 70-253, CP 04510, Mexico, D. F., Mexico.
authors.forename: Gustavo
authors.initials: G
authors.lastname: Sánchez-Chávez
authors.affiliation: División de Neurociencias, Departamento de Neurodesarrollo y Fisiología, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Apdo. Postal 70-253, CP 04510, Mexico, D. F., Mexico.
authors.forename: Ernesto
authors.initials: E
authors.lastname: Hernández-Ramírez
authors.affiliation: División de Neurociencias, Departamento de Neurodesarrollo y Fisiología, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Apdo. Postal 70-253, CP 04510, Mexico, D. F., Mexico.
authors.forename: Ixchel
authors.initials: I
authors.lastname: Osorio-Paz
authors.affiliation: División de Neurociencias, Departamento de Neurodesarrollo y Fisiología, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Apdo. Postal 70-253, CP 04510, Mexico, D. F., Mexico.
authors.forename: Claudia
authors.initials: C
authors.lastname: Hernández-Espinosa
authors.affiliation: División de Neurociencias, Departamento de Neurodesarrollo y Fisiología, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Apdo. Postal 70-253, CP 04510, Mexico, D. F., Mexico. rsalceda@ifc.unam.mx.
authors.forename: Rocío
authors.initials: R
authors.lastname: Salceda
mesh_terms: D000154:Aconitate Hydratase / Q000378:metabolism; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D003930:Diabetic Retinopathy / Q000378:metabolism*; D059865:Endoplasmic Reticulum Stress; D063928:Ependymoglial Cells / Q000378:metabolism; D005609:Free Radicals / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D015227:Lipid Peroxidation; D019255:NADPH Oxidases / Q000378:metabolism; D018384:Oxidative Stress; D020318:Rats, Long-Evans; D012160:Retina / Q000378:metabolism; D051742:Transcription Factor CHOP / Q000378:metabolism
chemical_list: D015415:Biomarkers; C497251:Ddit3 protein, rat; D005609:Free Radicals; D051742:Transcription Factor CHOP; D019255:NADPH Oxidases; D000154:Aconitate Hydratase; D005978:Glutathione
keywords: Carbonylation; Diabetes; Endoplasmic reticulum stress; Glutathione; NOX; Quercetin; Retina; Superoxide dismutase