title: Retinal gene expression and Müller cell responses after branch retinal vein occlusion in the rat.
abstract: OBJECTIVE
  In a rat model of branch retinal vein occlusion (BRVO), changes in gene expression of factors implicated in the development of retinal edema and alterations in the properties of Müller cells were determined.
  
  
  METHODS
  In adult Long-Evans rats, BRVO was induced by laser photocoagulation of retinal veins; untreated eyes served as controls. The mRNA levels of after factors were determined with real-time RT-PCR in the neural retina and retinal pigment epithelium after 1 and 3 days of BRVO: VEGF-A, pigment epithelium-derived factor (PEDF), tissue factor, prothrombin, the potassium channel Kir4.1, and aquaporins 1 and 4. Potassium currents were recorded in isolated Müller cells, and cellular swelling was assessed in retinal slices.
  
  
  RESULTS
  In the neural retina, the expression of VEGF was upregulated within 1 day of BRVO and returned to the control level after 3 days. PEDF was upregulated in the neuroretina and retinal pigment epithelium after 3 days of BRVO. Prothrombin, Kir4.1, and both aquaporins were downregulated in the neuroretina. After BRVO, Müller cells displayed a decrease in their potassium currents and an altered distribution of Kir4.1 protein, an increase in the size of their somata, and cellular swelling under hypoosmotic stress that was not observed in control tissues.
  
  
  CONCLUSIONS
  BRVO results in a rapid transient increase in the expression of VEGF and a delayed increase in the expression of PEDF. The downregulation of Kir4.1 and aquaporins, the mislocation of Kir4.1 protein, and the osmotic swelling of Müller cells may contribute to the development of edema and neuronal degeneration.
authors.affiliation: Department of Ophthalmology and Eye Hospital, University of Leipzig Faculty of Medicine, Liebigstrasse 10-14, 04103 Leipzig, Germany. matus.rehak@medizin.uni-leipzig.de
authors.forename: Matus
authors.initials: M
authors.lastname: Rehak
authors.forename: Margrit
authors.initials: M
authors.lastname: Hollborn
authors.forename: Ianors
authors.initials: I
authors.lastname: Iandiev
authors.forename: Thomas
authors.initials: T
authors.lastname: Pannicke
authors.forename: Anett
authors.initials: A
authors.lastname: Karl
authors.forename: Antje
authors.initials: A
authors.lastname: Wurm
authors.forename: Leon
authors.initials: L
authors.lastname: Kohen
authors.forename: Andreas
authors.initials: A
authors.lastname: Reichenbach
authors.forename: Peter
authors.initials: P
authors.lastname: Wiedemann
authors.forename: Andreas
authors.initials: A
authors.lastname: Bringmann
mesh_terms: D000818:Animals; D051398:Aquaporin 1 / Q000235:genetics; D051401:Aquaporin 4 / Q000235:genetics; D004195:Disease Models, Animal; D004594:Electrophysiology; D005136:Eye Proteins / Q000235:genetics*; D019084:Fluorescent Antibody Technique, Indirect; D005786:Gene Expression Regulation / Q000502:physiology*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D008269:Macular Edema / Q000235:genetics / Q000378:metabolism; D008564:Membrane Potentials; D009414:Nerve Growth Factors / Q000235:genetics; D024661:Potassium Channels, Inwardly Rectifying / Q000235:genetics; D011516:Prothrombin / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D020318:Rats, Long-Evans; D012160:Retina / Q000378:metabolism*; D012162:Retinal Degeneration / Q000235:genetics / Q000378:metabolism; D055351:Retinal Neurons / Q000502:physiology*; D012170:Retinal Vein Occlusion / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015843:Serpins / Q000235:genetics; D013925:Thromboplastin / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics; D014746:Vimentin / Q000378:metabolism; D000098854:Kcnj10 Channel; D000099174:Pigment Epithelium-Derived Factor
chemical_list: D051398:Aquaporin 1; D051401:Aquaporin 4; D005136:Eye Proteins; D005904:Glial Fibrillary Acidic Protein; D009414:Nerve Growth Factors; D024661:Potassium Channels, Inwardly Rectifying; D011516:Prothrombin; D012333:RNA, Messenger; D015843:Serpins; D013925:Thromboplastin; D042461:Vascular Endothelial Growth Factor A; D014746:Vimentin; D000098854:Kcnj10 Channel; D000099174:Pigment Epithelium-Derived Factor; C496022:Aqp1 protein, rat; C496032:Aqp4 protein, rat; C467498:vascular endothelial growth factor A, rat