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Preliminary study of retinal pathological features in preterm birth pups exposed to an animal model of oxygen-induced retinopathy in mice

Background The main risk factors of retinopathy of prematurity (ROP) are low gestational age and low birth weight, which are mainly caused by preterm birth. Currently, the animal model of oxygen-induced retinopathy (OIR) in mice is the most widely used model in ROP-associated studies. However, the e...

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Published in:Graefe's archive for clinical and experimental ophthalmology 2013-08, Vol.251 (8), p.1937-1943
Main Authors: Chu, Zhao-jie, Dou, Guo-rui, Wang, Yu-sheng, Qu, Xiao-jie, Zhang, Ye
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Zhang, Ye
description Background The main risk factors of retinopathy of prematurity (ROP) are low gestational age and low birth weight, which are mainly caused by preterm birth. Currently, the animal model of oxygen-induced retinopathy (OIR) in mice is the most widely used model in ROP-associated studies. However, the experimental mice are normal-term pups, and may not mimic the pathogenic status of human ROP patients. In this study, we investigated the retinal pathological features in preterm birth pups exposed to an animal model of oxygen-induced retinopathy in mice. Methods Preterm-birth mice were obtained from pregnant C57BL/6J mice that were induced by an intraperitoneal injection of lipopolysaccharide (LPS). The preterm and control mice were treated with high oxygen (75 %) from postnatal day 7 (P7) to P12. The mice were perfused with high-molecular-weight FITC-dextran on P12, P15 and P17, and the retinas were whole-mounted and imaged. Vascular endothelial growth factor (VEGF) mRNA was also detected. Cross-sections of the retina were stained with hematoxylin and eosin (H&E) to identify preretinal neovascular tufts. For general observation, whole retinal images were also obtained using a microscope. Results Leakage of the retinal blood vessels was aggravated in the preterm mice, particularly on P12 and P15. The non-perfused areas of the retina (pixel value, 183,673 ± 28,148 vs 132,110 ± 23,732, P  = 0.009) and the number of preretinal endothelial cell nuclei were smaller (30.17 ± 8.33 vs 22.17 ± 6.74, P  
doi_str_mv 10.1007/s00417-013-2366-8
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Currently, the animal model of oxygen-induced retinopathy (OIR) in mice is the most widely used model in ROP-associated studies. However, the experimental mice are normal-term pups, and may not mimic the pathogenic status of human ROP patients. In this study, we investigated the retinal pathological features in preterm birth pups exposed to an animal model of oxygen-induced retinopathy in mice. Methods Preterm-birth mice were obtained from pregnant C57BL/6J mice that were induced by an intraperitoneal injection of lipopolysaccharide (LPS). The preterm and control mice were treated with high oxygen (75 %) from postnatal day 7 (P7) to P12. The mice were perfused with high-molecular-weight FITC-dextran on P12, P15 and P17, and the retinas were whole-mounted and imaged. Vascular endothelial growth factor (VEGF) mRNA was also detected. Cross-sections of the retina were stained with hematoxylin and eosin (H&amp;E) to identify preretinal neovascular tufts. For general observation, whole retinal images were also obtained using a microscope. Results Leakage of the retinal blood vessels was aggravated in the preterm mice, particularly on P12 and P15. The non-perfused areas of the retina (pixel value, 183,673 ± 28,148 vs 132,110 ± 23,732, P  = 0.009) and the number of preretinal endothelial cell nuclei were smaller (30.17 ± 8.33 vs 22.17 ± 6.74, P  &lt; 0.0001) on P17. The VEGF mRNA levels in the retinas were higher on P12 and P15 but lower on P17, compared with the control mice. Retinal hemorrhage was observed in the preterm mouse group (five out of six examined eyes). Conclusions Preterm-birth mice that were subject to OIR exhibited several pathological features, such as retinal hemorrhage, severe retinal leakage and moderate retinal neovascularization, which were similar to the clinical manifestations in ROP patients.</description><identifier>ISSN: 0721-832X</identifier><identifier>EISSN: 1435-702X</identifier><identifier>DOI: 10.1007/s00417-013-2366-8</identifier><identifier>PMID: 23740517</identifier><language>eng</language><publisher>Berlin/Heidelberg: Springer Berlin Heidelberg</publisher><subject>Animals ; Animals, Newborn ; Basic Science ; Capillary Permeability ; Dextrans - metabolism ; Disease Models, Animal ; Female ; Fluorescein-5-isothiocyanate - analogs &amp; derivatives ; Fluorescein-5-isothiocyanate - metabolism ; Medicine ; Medicine &amp; Public Health ; Mice ; Mice, Inbred C57BL ; Microscopy, Confocal ; Ophthalmology ; Oxygen - toxicity ; Pregnancy ; Real-Time Polymerase Chain Reaction ; Retinal Hemorrhage - diagnosis ; Retinal Hemorrhage - genetics ; Retinal Neovascularization - chemically induced ; Retinal Neovascularization - diagnosis ; Retinal Neovascularization - genetics ; Retinal Vessels - metabolism ; Retinal Vessels - pathology ; Retinopathy of Prematurity - chemically induced ; Retinopathy of Prematurity - diagnosis ; Retinopathy of Prematurity - genetics ; RNA, Messenger - metabolism ; Vascular Endothelial Growth Factor A - genetics ; Vascular Endothelial Growth Factor A - metabolism</subject><ispartof>Graefe's archive for clinical and experimental ophthalmology, 2013-08, Vol.251 (8), p.1937-1943</ispartof><rights>Springer-Verlag Berlin Heidelberg 2013</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c405t-3b09a3ab03b72754868ce848af3db226b8cfe1e223304b9e0f76c7c450a50fdf3</citedby><cites>FETCH-LOGICAL-c405t-3b09a3ab03b72754868ce848af3db226b8cfe1e223304b9e0f76c7c450a50fdf3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23740517$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Chu, Zhao-jie</creatorcontrib><creatorcontrib>Dou, Guo-rui</creatorcontrib><creatorcontrib>Wang, Yu-sheng</creatorcontrib><creatorcontrib>Qu, Xiao-jie</creatorcontrib><creatorcontrib>Zhang, Ye</creatorcontrib><title>Preliminary study of retinal pathological features in preterm birth pups exposed to an animal model of oxygen-induced retinopathy in mice</title><title>Graefe's archive for clinical and experimental ophthalmology</title><addtitle>Graefes Arch Clin Exp Ophthalmol</addtitle><addtitle>Graefes Arch Clin Exp Ophthalmol</addtitle><description>Background The main risk factors of retinopathy of prematurity (ROP) are low gestational age and low birth weight, which are mainly caused by preterm birth. Currently, the animal model of oxygen-induced retinopathy (OIR) in mice is the most widely used model in ROP-associated studies. However, the experimental mice are normal-term pups, and may not mimic the pathogenic status of human ROP patients. In this study, we investigated the retinal pathological features in preterm birth pups exposed to an animal model of oxygen-induced retinopathy in mice. Methods Preterm-birth mice were obtained from pregnant C57BL/6J mice that were induced by an intraperitoneal injection of lipopolysaccharide (LPS). The preterm and control mice were treated with high oxygen (75 %) from postnatal day 7 (P7) to P12. The mice were perfused with high-molecular-weight FITC-dextran on P12, P15 and P17, and the retinas were whole-mounted and imaged. Vascular endothelial growth factor (VEGF) mRNA was also detected. Cross-sections of the retina were stained with hematoxylin and eosin (H&amp;E) to identify preretinal neovascular tufts. For general observation, whole retinal images were also obtained using a microscope. Results Leakage of the retinal blood vessels was aggravated in the preterm mice, particularly on P12 and P15. The non-perfused areas of the retina (pixel value, 183,673 ± 28,148 vs 132,110 ± 23,732, P  = 0.009) and the number of preretinal endothelial cell nuclei were smaller (30.17 ± 8.33 vs 22.17 ± 6.74, P  &lt; 0.0001) on P17. The VEGF mRNA levels in the retinas were higher on P12 and P15 but lower on P17, compared with the control mice. Retinal hemorrhage was observed in the preterm mouse group (five out of six examined eyes). 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Currently, the animal model of oxygen-induced retinopathy (OIR) in mice is the most widely used model in ROP-associated studies. However, the experimental mice are normal-term pups, and may not mimic the pathogenic status of human ROP patients. In this study, we investigated the retinal pathological features in preterm birth pups exposed to an animal model of oxygen-induced retinopathy in mice. Methods Preterm-birth mice were obtained from pregnant C57BL/6J mice that were induced by an intraperitoneal injection of lipopolysaccharide (LPS). The preterm and control mice were treated with high oxygen (75 %) from postnatal day 7 (P7) to P12. The mice were perfused with high-molecular-weight FITC-dextran on P12, P15 and P17, and the retinas were whole-mounted and imaged. Vascular endothelial growth factor (VEGF) mRNA was also detected. Cross-sections of the retina were stained with hematoxylin and eosin (H&amp;E) to identify preretinal neovascular tufts. For general observation, whole retinal images were also obtained using a microscope. Results Leakage of the retinal blood vessels was aggravated in the preterm mice, particularly on P12 and P15. The non-perfused areas of the retina (pixel value, 183,673 ± 28,148 vs 132,110 ± 23,732, P  = 0.009) and the number of preretinal endothelial cell nuclei were smaller (30.17 ± 8.33 vs 22.17 ± 6.74, P  &lt; 0.0001) on P17. The VEGF mRNA levels in the retinas were higher on P12 and P15 but lower on P17, compared with the control mice. Retinal hemorrhage was observed in the preterm mouse group (five out of six examined eyes). Conclusions Preterm-birth mice that were subject to OIR exhibited several pathological features, such as retinal hemorrhage, severe retinal leakage and moderate retinal neovascularization, which were similar to the clinical manifestations in ROP patients.</abstract><cop>Berlin/Heidelberg</cop><pub>Springer Berlin Heidelberg</pub><pmid>23740517</pmid><doi>10.1007/s00417-013-2366-8</doi><tpages>7</tpages></addata></record>
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issn 0721-832X
1435-702X
language eng
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subjects Animals
Animals, Newborn
Basic Science
Capillary Permeability
Dextrans - metabolism
Disease Models, Animal
Female
Fluorescein-5-isothiocyanate - analogs & derivatives
Fluorescein-5-isothiocyanate - metabolism
Medicine
Medicine & Public Health
Mice
Mice, Inbred C57BL
Microscopy, Confocal
Ophthalmology
Oxygen - toxicity
Pregnancy
Real-Time Polymerase Chain Reaction
Retinal Hemorrhage - diagnosis
Retinal Hemorrhage - genetics
Retinal Neovascularization - chemically induced
Retinal Neovascularization - diagnosis
Retinal Neovascularization - genetics
Retinal Vessels - metabolism
Retinal Vessels - pathology
Retinopathy of Prematurity - chemically induced
Retinopathy of Prematurity - diagnosis
Retinopathy of Prematurity - genetics
RNA, Messenger - metabolism
Vascular Endothelial Growth Factor A - genetics
Vascular Endothelial Growth Factor A - metabolism
title Preliminary study of retinal pathological features in preterm birth pups exposed to an animal model of oxygen-induced retinopathy in mice
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