title: Inhibition of choroidal neovascularization by lentivirus-mediated PEDF gene transfer in rats.
abstract: OBJECTIVE
  To evaluate the effects of lentivirus-mediated pigment epithelium-derived factor (PEDF) gene transfer performed in treatment of rats with established choroidal neovascularization (CNV), and investigates the mechanism by which PEDF inhibits CNV in rats.
  
  
  METHODS
  Brown Norway (BN) rats (n=204) were induced by exposure to a laser, and then randomly assigned to 3 groups: no treatment; treatments with intravitreal injection of lentivirus-PEDF-green fluorescent protein (GFP) or lentivirus-control GFP (free fluorescent protein). Following induction and treatment, the CNV tissue was assessed for form, size and vessel leakage by fluorescein fundus angiography (FFA), optical coherence tomography (OCT), histopathology, and examination of choroidal flat mounts. VEGF, Flk-1, and PEDF expression were evaluated by real-time polymerase chain reaction (PCR) and Western blot.
  
  
  RESULTS
  A stable laser-induced rat model of CNV was successfully established, and used to demonstrate lentivirus-mediated PEDG gene transfer by intravitreal injection. Expression of green fluorescence labelled PEDF was observed in the retina up to 28d after injection. An intravitreal injection of lentivirus-PEDF-GFP at 7d led to a significant reduction in the size, thickness and area of CNV showed by FFA, OCT and choroidal flat mounts. PEDF was up-regulated while VEGF and Flk-1 were down-regulated in the lentivirus-PEDF-GFP group. The differences in VEGF and Flk-1 expression in the control and lentivirus-PEDF groups at 7, 14, 21 and 28d after laser induction were all statistically significant.
  
  
  CONCLUSIONS
  Lentivirus-mediated PEDF gene transfer is effective for use in treatment of laser-induced CNV, and PEDF exerts its therapeutic effects by inhibiting expression of VEGF and Flk-1.
authors: Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing Ophthalmology & Visual Sciences Key Laboratory, Beijing 100730, China.
authors: Ya-Jie
authors: YJ
authors: Yu
authors: Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing Ophthalmology & Visual Sciences Key Laboratory, Beijing 100730, China.
authors: Bin
authors: B
authors: Mo
authors: Department of Ophthalmology, Fuxing Hospital, Capital Medical University, Beijing 100038, China.
authors: Lu
authors: L
authors: Liu
authors: Department of Ophthalmology, Fuxing Hospital, Capital Medical University, Beijing 100038, China.
authors: Yan-Kun
authors: YK
authors: Yue
authors: Department of Pathology, Beijing Tongren Hospital, Capital Medical University, Beijing 100038, China.
authors: Chang-Li
authors: CL
authors: Yue
authors: Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing Ophthalmology & Visual Sciences Key Laboratory, Beijing 100730, China.
authors: Wu
authors: W
authors: Liu
keywords: Flk-1; choroidal neovascularization; lentivirus; pigment epithelium-derived factor; vascular endothelial growth factor