title: Implication of VEGF and aquaporin 4 mediating Müller cell swelling to diabetic retinal edema.
abstract: OBJECTIVE
  Aquaporin 4 (AQP4), a water channel protein, is known to be expressed in retinal Müller cells. The purpose of this study was to determine the effects of VEGF and AQP4 channels on the volumetric changes in Müller cells.
  
  
  METHODS
  Retinas from diabetic rats and a cultured Müller cell line, TR-MUL5, were used in this study. Intravitreal injections of VEGF or PBS were performed on either streptozotocin (STZ)-induced diabetic or normoglycemic rats. Retinal sections were immunostained for anti-glial fibrillary acidic protein (GFAP), anti-AQP4, and anti-VEGF. VEGF protein levels from collected retinas were determined by western blot analysis. Volumetric changes and nitric oxide (NO) levels in cultured Müller cells were determined using flow cytometry (FACS), in the presence or absence of VEGF and TGN-020, a selective AQP4 inhibitor.
  
  
  RESULTS
  In the diabetic rat retina, VEGF immunoreactivity was concentrated in the internal retinal layers, and AQP4 immunoreactivity was higher than controls. The expressions of AQP4 were colocalized with GFAP. Protein levels of VEGF in the hyperglycemic rat retina were significantly higher than controls. FACS analyses showed that exposure to VEGF enlarged Müller cells, while exposure to TGN-020 suppressed the enlargement. Intracellular levels of NO were increased after exposure to VEGF, which was suppressed following the addition of TGN-020.
  
  
  CONCLUSIONS
  The observed Müller cell swelling is mediated by VEGF and AQP4.
authors.affiliation: Department of Ophthalmology, Osaka Medical College, 2-7 Daigaku-machi, Takatsuki, Osaka, 569-8686, Japan. kidateruyo@gmail.com.
authors.forename: Teruyo
authors.initials: T
authors.lastname: Kida
authors.affiliation: Department of Ophthalmology, Osaka Medical College, 2-7 Daigaku-machi, Takatsuki, Osaka, 569-8686, Japan.
authors.forename: Hidehiro
authors.initials: H
authors.lastname: Oku
authors.affiliation: Department of Ophthalmology, Osaka Medical College, 2-7 Daigaku-machi, Takatsuki, Osaka, 569-8686, Japan.
authors.forename: Taeko
authors.initials: T
authors.lastname: Horie
authors.affiliation: Department of Ophthalmology, Osaka Medical College, 2-7 Daigaku-machi, Takatsuki, Osaka, 569-8686, Japan.
authors.forename: Masanori
authors.initials: M
authors.lastname: Fukumoto
authors.affiliation: Department of Ophthalmology, Osaka Medical College, 2-7 Daigaku-machi, Takatsuki, Osaka, 569-8686, Japan.
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Okuda
authors.affiliation: Department of Ophthalmology, Osaka Medical College, 2-7 Daigaku-machi, Takatsuki, Osaka, 569-8686, Japan.
authors.forename: Seita
authors.initials: S
authors.lastname: Morishita
authors.affiliation: Department of Ophthalmology, Osaka Medical College, 2-7 Daigaku-machi, Takatsuki, Osaka, 569-8686, Japan.
authors.forename: Tsunehiko
authors.initials: T
authors.lastname: Ikeda
mesh_terms: D000818:Animals; D051401:Aquaporin 4 / Q000096:biosynthesis / Q000235:genetics*; D015153:Blotting, Western; D002478:Cells, Cultured; D003921:Diabetes Mellitus, Experimental; D003930:Diabetic Retinopathy / Q000150:complications / Q000235:genetics* / Q000473:pathology; D063928:Ependymoglial Cells / Q000378:metabolism* / Q000473:pathology; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D007150:Immunohistochemistry; D008297:Male; D010211:Papilledema / Q000175:diagnosis / Q000209:etiology / Q000235:genetics*; D051381:Rats; D017208:Rats, Wistar; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis / Q000235:genetics*
chemical_list: D051401:Aquaporin 4; D042461:Vascular Endothelial Growth Factor A
keywords: Aquaporin 4; Müller cell; Retinal edema; Streptozotocin (STZ) induced hyperglycemic rat; VEGF