Vitreous Levels of Erythropoietin and Vascular Endothelial Growth Factor in Eyes with Retinopathy of Prematurity

Sato, Tatsuhiko; Kusaka, Shunji; Shimojo, Hiroshi; Fujikado, Takashi

doi:10.1016/j.ophtha.2008.12.023

Cited by 137 publications

(83 citation statements)

References 19 publications

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“…A clinical study, confirming the observations from animal studies, showed that vitreous EPO was elevated, along with vitreous VEGF, in patients with proliferative ROP (n = 20) [64] , and vitreous EPO was significantly higher (10-fold) than serum EPO, as reported by Bierer et al [71] , in infants with similar weight and gestational age (serum 26 8 11 vs. vitreous 601.9 8 233 mIU/ml). So it is possible that elevated retinal EPO is due to local production rather than diffusion from blood.…”

Section: B1(c) Elevated Levels Of Epo and Prevention Of Progression supporting

confidence: 80%

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A Paradigm Shift in the Prevention of Retinopathy of Prematurity

Raghuveer

Bloom²

2011

Neonatology

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For more than 50 years it has been known that oxygen therapy can lead to retinopathy of prematurity (ROP). Recent clinical research has led many neonatologists to lower the target oxygen saturation alarm limits to 85–93% and to titrate the inspired oxygen in small increments. Despite efforts to optimize oxygen therapy, the number of cases of severe ROP remains high as more extremely low birth weight infants survive. Based on new insights into the pathogenesis of ROP, there are multiple interventions, in addition to optimizing oxygen therapy that may help decrease severe ROP. Interventions that have the potential to prevent phase I ROP (birth to ≤32 weeks PMA) include increasing retinal erythropoietin (exogenous rHuEPO) and serum IGF-1 (breast milk and/or exogenous IGF-1), maintaining serum glucose below 120 mg, and providing omega-3 supplements. Interventions with potential to prevent proliferative ROP in phase II (infants >32–34 weeks PMA) include treating anemia with a liberal policy of transfusion in premature infants with stage III ROP, photopic adaptation, vitamin E supplements (>34 weeks PMA), and omega-3 supplements. The WINROP algorithm has shown promise as a biomarker in the early identification of extremely low birth weight infants at high risk for proliferative ROP. As there is interplay of multiple factors in the causation of ROP, we suggest that the simultaneous application of some combination of multiple interventions, mentioned above, may reduce the burden of ROP in the most vulnerable infants. These conceptsneed study in well-designed randomized clinical trials before being incorporated into clinical practice.

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Section: B1(c) Elevated Levels Of Epo and Prevention Of Progression supporting

confidence: 80%

“…Anemia occurs concurrently in many premature infants who develop proliferative ROP with elevated retinal EPO (and VEGF) [64] from retinal hypoxia. Decreased oxygen carrying capacity of blood with anemia can potentially exacerbate retinal hypoxia and further increase retinal EPO.…”

Section: B1(c) Elevated Levels Of Epo and Prevention Of Progression mentioning

confidence: 99%

A Paradigm Shift in the Prevention of Retinopathy of Prematurity

Raghuveer

Bloom²

2011

Neonatology

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“…After the landmark studies by Aiello and colleagues on the association of retinal neovascularization with the vascular endothelium growth factor (VEGF) in diabetic retinopathy and retinal vein occlusions (Aiello et al 1994(Aiello et al , 1995, consequent investigations showed the associations of VEGF with other neovascular diseases such as exudative AMD and retinopathy of prematurity (Kvanta et al 1996;Matsuoka et al 2004;Nonobe et al 2009;Sato et al 2009). Other studies revealed that besides VEGF, also other cytokines were found in elevated concentrations in the aqueous humour, vitreous and retina of eyes with neovascular disorders.…”

Section: Introductionmentioning

confidence: 99%

Cytokine concentration in aqueous humour of eyes with exudative age‐related macular degeneration

Jonas

Tao

Neumaier

et al. 2012

Acta Ophthalmologica

133

107

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ABSTRACT.Purpose: To measure the concentration of cytokines in the aqueous humour of eyes with exudative age-related macular degeneration (AMD). Methods: The clinical interventional study included a study group of 18 patients with exudative AMD and a control group of 20 patients undergoing routine cataract surgery. Age did not vary significantly (p = 0.36) between study group (80.8 ± 6.4 years) and control group (77.0 ± 9.9 years), nor did gender (p = 0.75). During the interventions, aqueous humour samples were obtained, in which the concentration of cytokines was measured using a solidphase chemiluminescence immunoassay. Macular thickness was measured by optical coherence tomography (OCT). Results: In the study group as compared to the control group, significantly higher concentrations were measured for epithelial growth factor (EGF) (p = 0.017), human growth factor (HGF) (p = 0.048), intercellular adhesion molecule-1 (ICAM1) (p = 0.028), interleukin 12p40 (IL12p40)

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“…VEGF is a key and well-known factor in the process of angiogenesis, which stimulates endothelial cell activation and proliferation (21)(22)(23). A previous study demonstrated a higher vitreous level of EPO in stage 4 ROP, which was significantly correlated with the level of VEGF in the vitreous chamber of the eyes (24). Moreover, VEGF has been suggested to mediate angiogenesis through erythropoiesis-stimulating factors (25).…”

Section: Discussionmentioning

confidence: 99%

Exogenous erythropoietin aggravates retinal neovascularizationin a murine model of proliferative retinopathy

Yang¹,

Zhang²,

He³

et al. 2017

Turk J Med Sci

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About 10-16 mouse pups were used per group, and both eyes were removed for experimental Background/aim: Erythropoietin (EPO) has been proven recently to be a critical mediator in retinal neovascularization (RNV). Previous studies have indicated that the use of recombinant human EPO (rEPO) is a high risk factor in the development of retinopathy of prematurity. In this study, we aimed to investigate the effect of rEPO administration on RNV and its underlying mechanism in a mouse model of oxygen-induced retinopathy (OIR). Materials and methods:A murine model of OIR was used to generate RNV. After daily intraperitoneal injection of rEPO from postnatal day 12 (P12), mice were euthanized at P17. Whole-mount retina staining was used to indicate the nonperfused area and neovascularization tufts. Preretinal neovascular cells were calculated through hematoxylin and eosin staining. The expression levels of vascular endothelial growth factor (VEGF) and inducible nitric oxide synthase (iNOS) were detected via western blot analysis. Results:We found that injection of rEPO promoted the severity of RNV. The areas of neovascular tufts and preretinal neovascular cells were increased after administration of rEPO. When mice were injected with rEPO, a dose-dependent upregulation in VEGF and iNOS was observed. Conclusion:The study indicates the proangiogenic role of EPO, suggesting that rEPO contributes to the pathogenesis of RNV.

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Vitreous Levels of Erythropoietin and Vascular Endothelial Growth Factor in Eyes with Retinopathy of Prematurity

Cited by 137 publications

References 19 publications

A Paradigm Shift in the Prevention of Retinopathy of Prematurity

A Paradigm Shift in the Prevention of Retinopathy of Prematurity

Cytokine concentration in aqueous humour of eyes with exudative age‐related macular degeneration

Exogenous erythropoietin aggravates retinal neovascularizationin a murine model of proliferative retinopathy

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