title: Novel role of erythropoietin in proliferative diabetic retinopathy.
abstract: Diabetic retinopathy is a leading cause of visual disturbance in adults. In proliferative diabetic retinopathy, ischemia-induced pathologic growth of new blood vessels often causes catastrophic loss of vision. Besides VEGF, the existence of another potent ischemia-induced angiogenic factor is postulated. Since ischemia-inducible erythropoietin (Epo) has recently been identified its angiogenic properties, we investigated its potential role during retinal angiogenesis in proliferative diabetic retinopathy (PDR). The vitreous Epo level in patients with PDR was significantly higher than that in nondiabetic patients. Multivariate logistic regression analyses indicated that Epo and VEGF were independently associated with PDR and that Epo was more strongly associated with PDR than VEGF. Blockade of Epo inhibits retinal neovascularization in vivo, and inhibits endothelial cell proliferation response to PDR vitreous in vitro. Our data provide strong evidence that erythropoietin is a potent retinal angiogenic factor independent of VEGF and is capable of stimulating ischemia-induced retinal angiogenesis in proliferative diabetic retinopathy. Inhibition of such molecular mechanisms in the retinal angiogenesis could be a new therapeutical strategy in halting or preventing pathologic angiogenesis in diabetic retinopathy.
authors.affiliation: Department of Ophthalmology and Visual Sciences, Kyoto University, Graduate School of Medicine, Japan. hitoshi@kuhp.kyoto-u.ac.jp
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Takagi
authors.forename: Daisuke
authors.initials: D
authors.lastname: Watanabe
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Suzuma
authors.forename: Masafumi
authors.initials: M
authors.lastname: Kurimoto
authors.forename: Izumi
authors.initials: I
authors.lastname: Suzuma
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Ohashi
authors.forename: Tomonari
authors.initials: T
authors.lastname: Ojima
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Murakami
mesh_terms: D003930:Diabetic Retinopathy / Q000473:pathology / Q000503:physiopathology*; D004797:Enzyme-Linked Immunosorbent Assay; D004921:Erythropoietin / Q000235:genetics / Q000502:physiology*; D006801:Humans; D009389:Neovascularization, Pathologic / Q000517:prevention & control; D012333:RNA, Messenger / Q000235:genetics; D012171:Retinal Vessels / Q000503:physiopathology; D014652:Vascular Diseases / Q000503:physiopathology; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000502:physiology
chemical_list: D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D004921:Erythropoietin