title: Potential role of Cyr61 induced degeneration of human Müller cells in diabetic retinopathy.
abstract: 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<0.01). In retinal Müller cells culture, high glucose significantly and dose-dependently elevated Cyr61 expression at both mRNA and protein levels. Cyr61 at high concentrations dose-dependently inhibited the viability and migration of Müller cells. TUNEL assay further revealed that high concentration of Cyr61 significantly promoted the cell apoptosis. In conclusion, these findings demonstrated for the first time that the expression of Cyr61 was elevated by high glucose in Müller cells, and Cyr61 inhibited cell viability and migration while induced apoptosis, suggesting the potential role of Cyr61 in Müller cell degeneration. The elevated Cyr61 levels in vitreous fluid of PDR patients further support its role in diabetic retinopathy (DR).
authors.affiliation: Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China.
authors.forename: Fen
authors.initials: F
authors.lastname: Zhou
authors.affiliation: Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China.
authors.forename: Yikui
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China.
authors.forename: Ding
authors.initials: D
authors.lastname: Chen
authors.affiliation: Eye Center, Second Affiliated Hospital, College of Medicine, Zhejiang University, China.
authors.forename: Zhitao
authors.initials: Z
authors.lastname: Su
authors.affiliation: Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Jin
authors.affiliation: Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.affiliation: Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China.
authors.forename: Zhixiang
authors.initials: Z
authors.lastname: Hu
authors.affiliation: Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China.
authors.forename: Zhisheng
authors.initials: Z
authors.lastname: Ke
authors.affiliation: Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China.
authors.forename: Zongming
authors.initials: Z
authors.lastname: Song
mesh_terms: D000368:Aged; D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D055515:Cysteine-Rich Protein 61 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D003930:Diabetic Retinopathy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D063928:Ependymoglial Cells / Q000187:drug effects / Q000473:pathology*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D005947:Glucose / Q000494:pharmacology; D006801:Humans; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014822:Vitreous Body / Q000187:drug effects / Q000378:metabolism
chemical_list: D055515:Cysteine-Rich Protein 61; D012333:RNA, Messenger; D005947:Glucose