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Previous Volume 353:782-792 August 25, 2005 Number 8 Next

	Full Text PDF PDA Full Text PowerPoint Slide Set Editorial by Aiello, L. P. Letters Add to Personal Archive Add to Citation Manager Notify a Friend E-mail When Cited E-mail When Letters Appear PubMed Citation

ABSTRACT

Background 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<0.001). The median VEGF level in patients with retinopathy was also significantly higher than that in patients without diabetes (345.0 vs. 3.9 pg per milliliter, P<0.001). Multivariate logistic-regression analyses indicated that erythropoietin and VEGF were independently associated with proliferative diabetic retinopathy and that erythropoietin was more strongly associated with the presence of proliferative diabetic retinopathy than was VEGF. Erythropoietin and VEGF gene-expression levels are up-regulated in the murine ischemic retina, and the blockade of erythropoietin inhibits retinal neovascularization in vivo and endothelial-cell proliferation in the vitreous of patients with diabetic retinopathy in vitro.

Conclusions Our data suggest that erythropoietin is a potent ischemia-induced angiogenic factor that acts independently of VEGF during retinal angiogenesis in proliferative diabetic retinopathy.

Source Information

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{at}kuhp.kyoto-u.ac.jp.

Full Text of this Article

Related Letters:

Erythropoietin as a Retinal Angiogenic Factor
Manzoni P., Maestri A., Gomirato G., Takagi H., Watanabe D., Matsui S.
Extract | Full Text | PDF  
N Engl J Med 2005; 353:2190-2191, Nov 17, 2005. Correspondence

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