Erythropoietin as a Retinal Angiogenic Factor
http://www.100md.com
《新英格兰医药杂志》
To the Editor: Watanabe et al. (Aug. 25 issue)1 reported on erythropoietin as a factor inducing retinal angiogenesis in proliferative diabetic retinopathy independently of vascular endothelial growth factor. Preterm infants are at high risk for retinopathy of prematurity — a multifactorial, severe, vasoproliferative retinal disorder — and they often undergo treatment with erythropoietin for the prevention of anemia of prematurity.
In our tertiary neonatal intensive care unit in a high-income urban area in northern Italy, data on 695 neonates with birth weights of less than 1500 g who were admitted between 1997 and 2004 showed that erythropoietin is an additional, independent predictor of severe threshold retinopathy of prematurity (i.e., retinopathy requiring urgent ablative surgery) in the subgroup of extremely-low-birth-weight infants (weight less than 1000 g). Threshold retinopathy of prematurity occurred in 31.4 percent (54 of 172) of infants in this subgroup who received erythropoietin therapy, as compared with 19.6 percent (22 of 112) of those who did not receive erythropoietin (P=0.01 in the univariate analysis, P=0.04 in the multivariate analysis).
Many independent risk factors for retinopathy of prematurity have been identified in the literature,2 and erythropoietin has indeed been reported as responsible for this disorder in a murine model.3 Larger population-based studies should clarify whether erythropoietin also has a role in inducing severe retinopathy of prematurity in humans.
Paolo Manzoni, M.D.
Andrea Maestri, M.D.
Giovanna Gomirato, M.D.
Sant'Anna Obstetrics and Neonatology Hospital
10136 Turin, Italy
paolomanzoni@hotmail.com
References
Watanabe D, Suzuma K, Matsui S, et al. Erythropoietin as a retinal angiogenic factor in proliferative diabetic retinopathy. N Engl J Med 2005;353:782-792.
Darlow BA, Hutchinson JL, Henderson-Smart DJ, Donoghue DA, Simpson JM, Evans NJ. Prenatal risk factors for severe retinopathy of prematurity among very preterm infants of the Australian and New Zealand Neonatal Network. Pediatrics 2005;115:990-996.
Morita M, Ohneda O, Yamashita T, et al. HLF/HIF-2alpha is a key factor in retinopathy of prematurity in association with erythropoietin. EMBO J 2003;22:1134-1146.
The authors reply: Dr. Manzoni and colleagues provide clinical data showing that erythropoietin treatment might affect retinopathy of prematurity. Our data show that erythropoietin levels are up-regulated and that the blockade of endogenous erythropoietin inhibits retinal neovascularization in the murine ischemic retina. Administered indiscriminately, erythropoietin has been reported to restore retinal neovascularization in retinopathy of prematurity in hypoxia-inducible factor–knockout mice.1 These in vivo experimental data, together with the letter of Manzoni et al., strongly suggest that erythropoietin plays a substantial role in retinal angioproliferative responses in retinopathy of prematurity as well as in proliferative diabetic retinopathy and indicate that it is possible that systemic treatment with erythropoietin could enhance retinal neovascularization in human retinopathy of prematurity. Although anemia itself has not been established as a risk factor for retinopathy of prematurity,2 infants with anemia who need erythropoietin treatment could have systemic ischemia and thus have retinopathy of prematurity more often. Further population-based analyses that would include serum erythropoietin and hematocrit levels could clarify this point.
Hitoshi Takagi, M.D., Ph.D.
Hyogo Prefectural Amagasaki Hospital
Amagasaki 660-0828, Japan
hitoshi@kuhp.kyoto-u.ac.jp
Daisuke Watanabe, M.D., Ph.D.
Shigeyuki Matsui, Ph.D.
Kyoto University Graduate School of Medicine
Kyoto 606-8507, Japan
References
Morita M, Ohneda O, Yamashita T, et al. HLF/HIF-2alpha is a key factor in retinopathy of prematurity in association with erythropoietin. EMBO J 2003;22:1134-1146.
Brooks SE, Marcus DM, Gillis D, Pirie E, Johnson MH, Bhatia J. The effect of blood transfusion protocol on retinopathy of prematurity: a prospective, randomized study. Pediatrics 1999;104:514-518.
In our tertiary neonatal intensive care unit in a high-income urban area in northern Italy, data on 695 neonates with birth weights of less than 1500 g who were admitted between 1997 and 2004 showed that erythropoietin is an additional, independent predictor of severe threshold retinopathy of prematurity (i.e., retinopathy requiring urgent ablative surgery) in the subgroup of extremely-low-birth-weight infants (weight less than 1000 g). Threshold retinopathy of prematurity occurred in 31.4 percent (54 of 172) of infants in this subgroup who received erythropoietin therapy, as compared with 19.6 percent (22 of 112) of those who did not receive erythropoietin (P=0.01 in the univariate analysis, P=0.04 in the multivariate analysis).
Many independent risk factors for retinopathy of prematurity have been identified in the literature,2 and erythropoietin has indeed been reported as responsible for this disorder in a murine model.3 Larger population-based studies should clarify whether erythropoietin also has a role in inducing severe retinopathy of prematurity in humans.
Paolo Manzoni, M.D.
Andrea Maestri, M.D.
Giovanna Gomirato, M.D.
Sant'Anna Obstetrics and Neonatology Hospital
10136 Turin, Italy
paolomanzoni@hotmail.com
References
Watanabe D, Suzuma K, Matsui S, et al. Erythropoietin as a retinal angiogenic factor in proliferative diabetic retinopathy. N Engl J Med 2005;353:782-792.
Darlow BA, Hutchinson JL, Henderson-Smart DJ, Donoghue DA, Simpson JM, Evans NJ. Prenatal risk factors for severe retinopathy of prematurity among very preterm infants of the Australian and New Zealand Neonatal Network. Pediatrics 2005;115:990-996.
Morita M, Ohneda O, Yamashita T, et al. HLF/HIF-2alpha is a key factor in retinopathy of prematurity in association with erythropoietin. EMBO J 2003;22:1134-1146.
The authors reply: Dr. Manzoni and colleagues provide clinical data showing that erythropoietin treatment might affect retinopathy of prematurity. Our data show that erythropoietin levels are up-regulated and that the blockade of endogenous erythropoietin inhibits retinal neovascularization in the murine ischemic retina. Administered indiscriminately, erythropoietin has been reported to restore retinal neovascularization in retinopathy of prematurity in hypoxia-inducible factor–knockout mice.1 These in vivo experimental data, together with the letter of Manzoni et al., strongly suggest that erythropoietin plays a substantial role in retinal angioproliferative responses in retinopathy of prematurity as well as in proliferative diabetic retinopathy and indicate that it is possible that systemic treatment with erythropoietin could enhance retinal neovascularization in human retinopathy of prematurity. Although anemia itself has not been established as a risk factor for retinopathy of prematurity,2 infants with anemia who need erythropoietin treatment could have systemic ischemia and thus have retinopathy of prematurity more often. Further population-based analyses that would include serum erythropoietin and hematocrit levels could clarify this point.
Hitoshi Takagi, M.D., Ph.D.
Hyogo Prefectural Amagasaki Hospital
Amagasaki 660-0828, Japan
hitoshi@kuhp.kyoto-u.ac.jp
Daisuke Watanabe, M.D., Ph.D.
Shigeyuki Matsui, Ph.D.
Kyoto University Graduate School of Medicine
Kyoto 606-8507, Japan
References
Morita M, Ohneda O, Yamashita T, et al. HLF/HIF-2alpha is a key factor in retinopathy of prematurity in association with erythropoietin. EMBO J 2003;22:1134-1146.
Brooks SE, Marcus DM, Gillis D, Pirie E, Johnson MH, Bhatia J. The effect of blood transfusion protocol on retinopathy of prematurity: a prospective, randomized study. Pediatrics 1999;104:514-518.