Endoplasmic reticulum stress is implicated in retinal inflammation and diabetic retinopathy

• Published in: FEBS letters 2009-05, Vol.583 (9), p.1521-1527
• Main Authors: Li, Jingming, Wang, Joshua J., Yu, Qiang, Wang, Min, Zhang, Sarah X.
• Format: Article
• Language: English
• Subjects: 4-phenyl butyric acid; activating transcription factor; Animals; ATF; Base Sequence; Cells, Cultured; Diabetic retinopathy; Diabetic Retinopathy - metabolism; DNA Primers; eIF; endoplasmic reticulum; Endoplasmic Reticulum - metabolism; Endoribonucleases - metabolism; ER stress; eukaryotic initiation factor; Eukaryotic Initiation Factor-2 - metabolism; glucose regulated protein 78; GRP78; Heat-Shock Proteins - metabolism; HREC; Human retinal endothelial cell; human retinal endothelial cells; Humans; Immunohistochemistry; Inflammation; inositol-requiring enzyme 1α; IRE1α; Mice; Mice, Inbred C57BL; Molecular Chaperones - metabolism; OIR; Oxidative Stress - drug effects; Oxygen-induced retinopathy; PBA; PERK; Phenylbutyrates - pharmacology; PKR-like ER kinase; Protein-Serine-Threonine Kinases - metabolism; Retina - metabolism; Retinitis - metabolism; Reverse Transcriptase Polymerase Chain Reaction; TNF-α; Tumor Necrosis Factor-alpha - metabolism; tumor necrosis factor-α; Tunicamycin - pharmacology; unfolded protein response; UPR; vascular endothelial growth factor; Vascular Endothelial Growth Factor A - metabolism; VEGF; X-box binding protein 1; XBP1
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/j.febslet.2009.04.007

Diabetic retinopathy is a chronic low-grade inflammatory disease; however, the mechanisms remain elusive. In the present study, we demonstrated that endoplasmic reticulum (ER) stress was activated in the retina in animal models of diabetes and oxygen-induced retinopathy (OIR). Induction of ER stress by tunicamycin resulted in significantly increased expression of inflammatory molecules in the retina. Inhibition of ER stress by chemical chaperone 4-phenyl butyric acid ameliorated inflammation in cultured human retinal endothelial cells exposed to hypoxia, and in the retinas of diabetic and OIR mice. These findings indicate that ER stress is a potential mediator of retinal inflammation in diabetic retinopathy.