Erythropoietin as a Retinal Angiogenic Factor in Proliferative Diabetic Retinopathy

• Published in: The New England journal of medicine Vol. 353; no. 8; pp. 782 - 792
• Main Authors: Watanabe, Daisuke, Suzuma, Kiyoshi, Suzuma, Izumi, Matsui, Shigeyuki, Kurimoto, Masafumi, Kiryu, Junichi, Kita, Mihori, Ohashi, Hirokazu, Ojima, Tomonari, Murakami, Tomoaki, Kobayashi, Toshihiro, Masuda, Seiji, Nagao, Masaya, Yoshimura, Nagahisa, Takagi, Hitoshi
• Format: Journal Article
• Language: English
• Published: Boston, MA Massachusetts Medical Society 25-08-2005
• Subjects: Angiogenesis; Animals; Biological and medical sciences; Biotechnology; Case-Control Studies; Cattle; Cell culture; Cell growth; Cell Proliferation; Cells, Cultured; Diabetic retinopathy; Diabetic Retinopathy - drug therapy; Diabetic Retinopathy - pathology; Diabetic Retinopathy - physiopathology; Dose-Response Relationship, Drug; Erythropoietin - analysis; Erythropoietin - antagonists & inhibitors; Erythropoietin - metabolism; Extracellular Matrix Proteins; Female; General aspects; Humans; Ischemia; Logistic Models; Male; Medical sciences; Mice; Middle Aged; Myosin Heavy Chains; Nonmuscle Myosin Type IIB; Ophthalmology; Proteins - pharmacology; Receptors, Erythropoietin - physiology; Retina - cytology; Retina - drug effects; Retina - metabolism; Retinal Neovascularization - pathology; Retinal Neovascularization - physiopathology; Retinopathies; RNA, Messenger - metabolism; Up-Regulation; Vascular endothelial growth factor; Vascular Endothelial Growth Factor A - analysis; Vascular Endothelial Growth Factor A - antagonists & inhibitors; Vascular Endothelial Growth Factor A - metabolism; Vitreous Body - chemistry; Vitreous body disease; Endocrinopathy; Medicine; Eye disease; Retinopathy; Erythropoietin; Angiogenic factor; Polypeptide; Diabetes mellitus; Retina; Proliferative vitreoretinopathy
• ISSN: 0028-4793; 1533-4406
• DOI: 10.1056/NEJMoa041773

This study measured vitreous levels of erythropoietin and vascular endothelial growth factor (VEGF) in proliferative diabetic retinopathy and other eye diseases. Increased levels of erythropoietin and VEGF were independently associated with proliferative diabetic retinopathy. In vitro studies indicated that erythropoietin blockade inhibits retinal neovascularization. These data suggest that erythropoietin is a potent ischemia-induced angiogenic factor acting independently of VEGF during retinal angiogenesis in proliferative diabetic retinopathy.
These data suggest that erythropoietin is a potent ischemia-induced angiogenic factor acting independently of vascular endothelial growth factor during retinal angiogenesis in proliferative diabetic retinopathy.
Pathologic growth of new blood vessels is a common final pathway in ocular neovascular diseases, such as proliferative diabetic retinopathy, that often result in catastrophic loss of vision. Vascular endothelial growth factor (VEGF) is a primary angiogenic factor that mediates such ischemia-induced retinal neovascularization. VEGF levels are elevated in the vitreous fluid of patients with proliferative diabetic retinopathy, and VEGF induces proliferation in vascular endothelial cells in vitro.
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Although inhibition of VEGF reduces retinal neovascularization,
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,
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it does not completely inhibit ischemia-driven retinal neovascularization. Thus, the involvement of other angiogenic factors in this process seems likely.
The glycoprotein erythropoietin stimulates . . .