title: CNTF Attenuates Vasoproliferative Changes Through Upregulation of SOCS3 in a Mouse-Model of Oxygen-Induced Retinopathy.
abstract: Retinal vascular disease represents a major cause for vision loss in the Western world. Recent research has shown that neuronal and vascular damage are closely related in retinal disease. Ciliary neurotrophic factor (CNTF) is a well-studied neurotrophic factor that is currently being tested in clinical trials for the treatment of retinal degenerative diseases and macular telangiectasia. However, little is known about its effect on retinal vasculature. In this study, we investigate the effects of CNTF in retinal neovascular disease using the mouse model of oxygen-induced retinopathy (OIR).
  
  
  
  Newborn pups were exposed to 75% oxygen from postnatal day (P)7 to P12 and subsequently returned to room air. Ciliary neurotrophic factor was injected intravitreally at OIR P12 and the vaso-obliterated and neovascular areas were quantified at OIR P17. Immunohistochemistry, RNA, and protein analysis were used to identify CNTF-responsive cells. In vitro experiments were performed to analyze the effect of CNTF on endothelial and astroglial cells.
  
  
  
  In the OIR model, CNTF facilitated capillary regrowth and attenuated preretinal neovascularization in a dose-dependent manner. The protective effect of CNTF was mediated via activation of the JAK/STAT3/SOCS3 signaling pathway. Immunohistochemical studies identified endothelial cells among others as CNTF-responsive cells in the retina. In vitro studies confirmed the anti-angiogenic effect of CNTF on endothelial cell sprouting.
  
  
  
  This study provides evidence for a therapeutic potential of CNTF beyond degenerative retinal disease. Vasoproliferative retinopathies may benefit from a CNTF-dependent and SOCS3-mediated angiomodulatory effect.
authors: Eye Center Medical Center, Faculty of Medicine, University of Freiburg, Germany 2Department of Cell and Molecular Biology, The Scripps Research Institute, La Jolla, California, United States.
authors: Felicitas
authors: F
authors: Bucher
authors: Eye Center Medical Center, Faculty of Medicine, University of Freiburg, Germany 3Department of Pharmacology and Toxicology, University of Regensburg, Regensburg, Germany.
authors: Johanna M
authors: JM
authors: Walz
authors: Eye Center Medical Center, Faculty of Medicine, University of Freiburg, Germany.
authors: Anima
authors: A
authors: Bühler
authors: Department of Cell and Molecular Biology, The Scripps Research Institute, La Jolla, California, United States.
authors: Edith
authors: E
authors: Aguilar
authors: Eye Center Medical Center, Faculty of Medicine, University of Freiburg, Germany.
authors: Clemens
authors: C
authors: Lange
authors: Department of Cell and Molecular Biology, The Scripps Research Institute, La Jolla, California, United States.
authors: Sophia
authors: S
authors: Diaz-Aguilar
authors: Eye Center Medical Center, Faculty of Medicine, University of Freiburg, Germany.
authors: Gottfried
authors: G
authors: Martin
authors: Eye Center Medical Center, Faculty of Medicine, University of Freiburg, Germany.
authors: Günther
authors: G
authors: Schlunck
authors: Eye Center Medical Center, Faculty of Medicine, University of Freiburg, Germany.
authors: Hansjürgen
authors: H
authors: Agostini
authors: Department of Cell and Molecular Biology, The Scripps Research Institute, La Jolla, California, United States.
authors: Martin
authors: M
authors: Friedlander
authors: Eye Center Medical Center, Faculty of Medicine, University of Freiburg, Germany.
authors: Andreas
authors: A
authors: Stahl
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D020934:Ciliary Neurotrophic Factor / Q000494:pharmacology*; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005786:Gene Expression Regulation; D006801:Humans; D007150:Immunohistochemistry; D008810:Mice, Inbred C57BL; D010100:Oxygen / Q000633:toxicity; D016133:Polymerase Chain Reaction; D012313:RNA / Q000235:genetics; D011994:Recombinant Proteins / Q000494:pharmacology; D012162:Retinal Degeneration / Q000139:chemically induced / Q000175:diagnosis / Q000188:drug therapy*; D015861:Retinal Neovascularization / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D012171:Retinal Vessels / Q000187:drug effects / Q000473:pathology*; D015398:Signal Transduction; D000071223:Suppressor of Cytokine Signaling 3 Protein / Q000096:biosynthesis / Q000235:genetics*; D015854:Up-Regulation
chemical_list: D020934:Ciliary Neurotrophic Factor; D011994:Recombinant Proteins; C491411:Socs3 protein, mouse; D000071223:Suppressor of Cytokine Signaling 3 Protein; D012313:RNA; D010100:Oxygen