Potential role of Cyr61 induced degeneration of human Müller cells in diabetic retinopathy

• Published in: PloS one 2014-10, Vol.9 (10), p.e109418
• Main Authors: Zhou, Fen, Zhang, Yikui, Chen, Ding, Su, Zhitao, Jin, Ling, Wang, Lei, Hu, Zhixiang, Ke, Zhisheng, Song, Zongming
• Format: Article
• Language: English
• Subjects: Active control; Aged; Apoptosis; Apoptosis - drug effects; Assaying; Biology and Life Sciences; Cell culture; Cell Line; Cell migration; Cell Movement - drug effects; Cell Survival - drug effects; CYR61 protein; Cysteine-Rich Protein 61 - biosynthesis; Cysteine-Rich Protein 61 - genetics; Cysteine-Rich Protein 61 - metabolism; Degeneration; Diabetes; Diabetes mellitus; Diabetic retinopathy; Diabetic Retinopathy - genetics; Diabetic Retinopathy - metabolism; Diabetic Retinopathy - pathology; Edema; Enzyme-linked immunosorbent assay; Ependymoglial Cells - drug effects; Ependymoglial Cells - pathology; Extracellular matrix; Female; Fibroblasts; Gene expression; Gene Expression Regulation - drug effects; Glucose; Glucose - pharmacology; Hospitals; Humans; Male; Medicine and Health Sciences; Middle Aged; mRNA; Pathogenesis; Pathology; Patients; Photoreceptors; Physical Sciences; Proteins; Retina; Retinopathy; RNA, Messenger - genetics; RNA, Messenger - metabolism; Rodents; Signaling; Surgery; Vascular endothelial growth factor; Vitreous Body - drug effects; Vitreous Body - metabolism
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0109418

The degeneration of Müller cells has been recognized to involve in the pathogenesis of diabetic retinopathy. However, the mechanism is not yet clear. This study is to explore the potential role of Cyr61, a secreted signaling protein in extracellular matrix, in inducing human Müller cell degeneration in diabetic retinopathy (DR). Twenty patients with proliferative diabetic retinopathy (PDR) and twelve non-diabetic patients were recruited for this study. Vitreous fluid was collected during vitrectomy surgery for Cyr61 ELISA. Human Müller cell line MIO-M1 were cultured to be subconfluent, and then treated with glucose (0-20 mM) or Cyr61 (0-300 ng/ml). Cyr61 expression induced by increasing concentrations of glucose was evaluated by RT-qPCR and Western blot. Effects of Cyr61 on Müller cells viability, migration and apoptosis were observed by MTT assay, Transwell assay, and TUNEL assay. Vitreous Cyr61 levels were observed to be 8-fold higher in patients with PDR (3576.92 ± 1574.58 pg/mL), compared with non-diabetic controls (436.14 ± 130.69 pg/mL). Interestingly, the active PDR group was significantly higher than the quiescent PDR group (P