Erythropoietin Implicated as Angiogenic Factor in Diabetic Retinopathy

New research indicates that erythropoietin is an independent promoter of retinal angiogenesis in proliferative diabetic retinopathy. This suggests that erythropoietin blockade may be a useful treatment for this common eye disorder.

Vascular endothelial growth factor (VEGF) has been identified as the principal mediator of retinal angiogenesis. However, simply inhibiting VEGF does not prevent retinal neovascularization, suggesting that other factors also play a role. Erythropoietin is known to have angiogenic activity, but its effect on ocular angiogenesis has been unclear.

To investigate, Dr. Hitoshi Takagi, from Kyoto University in Japan, and colleagues measured erythropoietin and VEGF levels in vitreous fluid samples obtained from 73 patients with proliferative diabetic retinopathy and 71 with nondiabetic ocular disease. The researchers used a murine model of ischemia-induced retinal neovascularization to further assess erythropoietin expression and regulation.

Vitreous levels of erythropoietin and VEGF were significantly higher in the diabetic group than in the nondiabetic group, the researchers note (p < 0.001 for both). Multivariate analysis showed that erythropoietin and, to a lesser extent, VEGF were independently linked to proliferative diabetic retinopathy.

In the murine model, erythropoietin and VEGF expression were increased in ischemic retina. Erythropoietin inhibition blocked retinal neovascularization in the model and reduced endothelial-cell proliferation in the vitreous of diabetic retinopathy patients.
These findings “regarding erythropoietin emphasize that (ophthalmic care of diabetic patients) should take into account not only VEGF but also other factors that may play a substantial role in the processes that threaten sight,” Dr. Lloyd Paul Aiello, from Harvard Medical School in Boston, notes in an accompanying editorial.

N Engl J Med 2005;353:782-792,839-841.