title: Overexpression of pigment epithelium-derived factor inhibits retinal inflammation and neovascularization.
abstract: Pigment epithelium-derived factor (PEDF) is a serine proteinase inhibitor with antiangiogenic activities. To investigate whether PEDF overexpression has an impact on ocular neovascularization in vivo, we generated PEDF transgenic (PEDF-Tg) mice that ubiquitously express human PEDF driven by the β-actin promoter. The PEDF-Tg mice under normal conditions did not show any abnormalities in retinal histologic findings or visual function. In contrast, PEDF-Tg animals with oxygen-induced retinopathy (OIR) developed significantly less severe retinal neovascularization compared with wild-type (Wt) mice with OIR. In addition, PEDF-Tg mice with OIR had significantly lower vascular leakage in the retina but higher occludin levels than the Wt mice with OIR, suggesting a protective effect on the blood-retinal barrier. Furthermore, retinal levels of proinflammatory factors were significantly lower in PEDF-Tg mice with OIR than in the Wt mice with OIR. In the laser-induced choroidal neovascularization (CNV) model, the CNV area was significantly smaller in the PEDF-Tg mice than in the Wt mice. Also, the laser burn-induced overexpression of proangiogenic and inflammatory factors was observed in the retina and retinal pigment epithelium of Wt mice but not in PEDF-Tg mice. Taken together, these results suggest that overexpression of PEDF inhibits retinal inflammation and neovascularization in both the OIR and laser-induced CNV models. The PEDF-Tg mice provide a useful model for studying the roles of angiogenic inhibitors in neovascular disorders such as diabetic retinopathy.
authors.affiliation: Department of Physiology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA.
authors.forename: Kyoungmin
authors.initials: K
authors.lastname: Park
authors.forename: Ji
authors.initials: J
authors.lastname: Jin
authors.forename: Yang
authors.initials: Y
authors.lastname: Hu
authors.forename: Kevin
authors.initials: K
authors.lastname: Zhou
authors.forename: Jian-xing
authors.initials: JX
authors.lastname: Ma
mesh_terms: D043925:Angiogenesis Inducing Agents / Q000378:metabolism; D000818:Animals; D020256:Choroidal Neovascularization / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D005136:Eye Proteins / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000378:metabolism* / Q000473:pathology*; D018836:Inflammation Mediators / Q000378:metabolism; D007511:Ischemia / Q000378:metabolism / Q000473:pathology; D007834:Lasers; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009414:Nerve Growth Factors / Q000378:metabolism*; D012160:Retina / Q000378:metabolism* / Q000473:pathology* / Q000503:physiopathology; D015861:Retinal Neovascularization / Q000378:metabolism* / Q000473:pathology*; D015843:Serpins / Q000378:metabolism*; D019076:Transgenes / Q000235:genetics; D000099174:Pigment Epithelium-Derived Factor
chemical_list: D043925:Angiogenesis Inducing Agents; D005136:Eye Proteins; D018836:Inflammation Mediators; D009414:Nerve Growth Factors; D015843:Serpins; D000099174:Pigment Epithelium-Derived Factor