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Erythropoietin as a Retinal Angiogenic Factor in Proliferative Diabetic Retinopathy

June 19, 2017 | Autor: Masafumi Kurimoto | Categoría: Gene expression, England, Logistic Regression, Erythropoietin, Humans, Mice, Diabetic Retinopathy, Female, Animals, Male, Retina, Proteins, Cattle, Middle Aged, New England, Endothelial cell, Cell Proliferation, Murine Model, New England Journalof Medicine, Enzyme Linked Immunosorbent Assay, Logistic Models, Radioimmunoassay, Vascular Endothelial Growth Factor, Extracellular Matrix Proteins, Case Control Studies, Mice, Diabetic Retinopathy, Female, Animals, Male, Retina, Proteins, Cattle, Middle Aged, New England, Endothelial cell, Cell Proliferation, Murine Model, New England Journalof Medicine, Enzyme Linked Immunosorbent Assay, Logistic Models, Radioimmunoassay, Vascular Endothelial Growth Factor, Extracellular Matrix Proteins, Case Control Studies
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The

new england journal

of

medicine

original article

Erythropoietin as a Retinal Angiogenic Factor in Proliferative Diabetic Retinopathy Daisuke Watanabe, M.D., Ph.D., Kiyoshi Suzuma, M.D., Ph.D., Shigeyuki Matsui, Ph.D., Masafumi Kurimoto, M.D., Junichi Kiryu, M.D., Ph.D., Mihori Kita, M.D., Ph.D., Izumi Suzuma, M.D., Ph.D., Hirokazu Ohashi, M.D., Ph.D., Tomonari Ojima, M.D., Tomoaki Murakami, M.D., Toshihiro Kobayashi, Ph.D., Seiji Masuda, Ph.D., Masaya Nagao, Ph.D., Nagahisa Yoshimura, M.D., Ph.D., and Hitoshi Takagi, M.D., Ph.D.

abstract

background From the Department of Ophthalmology and Visual Sciences, Kyoto University Graduate School of Medicine, Kyoto (D.W., K.S., M. Kurimoto, J.K., M. Kita, I.S., H.O., T.O., T.M., N.Y., H.T.); the Department of Pharmacoepidemiology, Kyoto University Graduate School of Public Health, Kyoto (S. Matsui); the Laboratory of Biosignals and Response, Kyoto University Graduate School of Biostudies, Kyoto (T.K., S. Masuda, M.N.); the Department of Ophthalmology, Otsu Red Cross Hospital, Otsu (M. Kita); and the Department of Ophthalmology, Hyogo Prefectural Amagasaki Hospital, Amagasaki (H.T.) — all in Japan. Address reprint requests to Dr. Takagi at the Department of Ophthalmology, Hyogo Prefectural Amagasaki Hospital, Higashidaimotsu-cho, 1-1-1, Amagasaki 660-0828, Japan, or at hitoshi@ kuhp.kyoto-u.ac.jp. N Engl J Med 2005;353:782-92. Copyright © 2005 Massachusetts Medical Society.

Although vascular endothelial growth factor (VEGF) is a primary mediator of retinal angiogenesis, VEGF inhibition alone is insufficient to prevent retinal neovascularization. Hence, it is postulated that there are other potent ischemia-induced angiogenic factors. Erythropoietin possesses angiogenic activity, but its potential role in ocular angiogenesis is not established. methods

We measured both erythropoietin and VEGF levels in the vitreous fluid of 144 patients with the use of radioimmunoassay and enzyme-linked immunosorbent assay. Vitreous proliferative potential was measured according to the growth of retinal endothelial cells in vitro and with soluble erythropoietin receptor. In addition, a murine model of ischemia-induced retinal neovascularization was used to evaluate erythropoietin expression and regulation in vivo. results

The median vitreous erythropoietin level in 73 patients with proliferative diabetic retinopathy was significantly higher than that in 71 patients without diabetes (464.0 vs. 36.5 mIU per milliliter, P
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