Exogenous erythropoietin aggravates retinal neovascularizationin a murine model of proliferative retinopathy

Abstract

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.

Intraocular injection of KH902 alleviates retinal hypoxia in a mouse model of oxygen-induced retinopathy

“…The Laboratory Animal Center of Wuhan University provided the C57BL/6J mice. An OIR mouse model was generated as previously described [20,21,24,25]. Briefly, at postnatal day 7 (P7), newborn pups were exposed to an environment of oxygen at 75±2% for 5 days and then returned to room air (RA).…”

“…As previously reported [21,24,25], 4% paraformaldehyde (PFA) was used to fix the removed eyes for 24 h, which were embedded in paraffin. Eyeballs were cut serially (6 μm).…”

The Genetics of Retinopathy of Prematurity: A Model for Neovascular Retinal Disease

“…Increased erythropoietin receptor signaling has also been shown to influence severe OIR models of disease through VEGFR2-mediated angiogenesis, making it an important target for clinical research in human patients. 99,100 While a variant of EPO was investigated in a candidate-gene study by Mohamed et. al., significance for this variant was not reported in the study results.…”

Erythropoietin and retinopathy of prematurity: a retrospective cohort study in Japan, 2008-2018

“…Early gestational age, low birth weight, and unregulated oxygen exposure are known to be risk factors for the ROP development [5,6]. Erythropoietin has an angiogenic effect on the retina, and animal studies reported that it might increase the risk of ROP [7,8]. Some previous human studies have reported an association between erythropoietin use and increased risk of ROP [9]; however, other studies found no associations [10][11][12].…”