In-vivo Retinal Vascular Oxygen Tension Imaging and Fluorescein Angiography in the Mouse Model of Oxygen-Induced Retinopathy.
ABSTRACT Purpose: Oxygenation abnormalities are implicated in the development of retinopathy of prematurity (ROP). The purpose of this study is to report in vivo retinal vascular oxygen tension (PO2) measurements and fluorescein angiography (FA) findings in the mouse model of oxygen-induced retinopathy (OIR). Methods: Nineteen neonatal mice were exposed to 77% oxygen from postnatal day 7 (P7) to P12 (OIR). Eleven neonatal mice were kept under room air (control). Using phosphorescence lifetime imaging, retinal vascular PO2 was measured followed by FA. Repeated measures ANOVA was performed to determine the effects of blood vessel type (artery and vein) and group (OIR and control) on PO2. Avascular retinal areas were measured from FA images in OIR mice. Results: There was a significant effect of vessel type on PO2 (p<0.001). The effect of group on PO2 was not significant (p=0.3), indicating similar PO2 between OIR and control mice. The interaction between group and vessel type was significant (p=0.03), indicating a larger arteriovenous PO2 difference in OIR mice than control mice. In control mice, FA displayed normal vascularization, while FA of OIR mice showed abnormalities including dilation and tortuosity of major retinal blood vessels and avascular regions. In OIR mice, the mean percent avascular retinal area was 33 ± 18%. Conclusions: In vivo assessment of retinal vascular oxygen tension and vasculature patterns demonstrated abnormalities in the mouse model of OIR. This approach has the potential to improve understanding of retinal vascular development and oxygenation alterations due to ROP and other ischemic retinal diseases.
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Article: MR studies of retinal oxygenation.[Show abstract] [Hide abstract]
ABSTRACT: In this paper, we summarize the development and application of two novel magnetic resonance based measurements of retinal oxygenation in experimental models of retinopathy, including diabetic retinopathy and retinopathy of prematurity. We use 19F-NMR and a small (microl) perfluorocarbon drop positioned in the preretinal vitreous space to make PO2 measurement of the inner retina. In addition, we use magnetic resonance imaging (MRI) to accurately and non-invasively measure the change in the preretinal PO2 (DeltaPO2) following the shift from breathing room air to a hyperoxic inhalation challenge. The advantages and disadvantages of each method are discussed. New applications of these techniques in the newborn rat and adult mouse are presented. We expect such studies to motivate future MRI oxygenation studies of human retinopathy, including diabetic retinopathy and retinopathy of prematurity.Vision Research 02/2001; 41(10-11):1307-11. · 2.38 Impact Factor
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ABSTRACT: To investigate the effects of prolonged hyperoxia on vascular recovery and glia survival after experimentally induced retinopathy of prematurity (ROP) in the mouse. The effects of hyperoxia on revascularization and vitreous neovascularization were compared between mice raised in 75% oxygen from postnatal day (P)7 to P12, followed by room air recovery and mice raised in 75% oxygen from P7 to P27. The status of astrocytes and Müller cells was evaluated by glial fibrillary acidic protein (GFAP) immunohistochemistry on retinal wholemounts and serial sections. A window of susceptibility to oxygen-induced vaso-obliteration was defined by comparing the extent of retinal vaso-obliteration resulting from 2 days of hyperoxia beginning on P7, P9, P11, P13, or P15. Oxygen-induced vaso-obliteration of retinal capillaries was limited to the period between birth and P15. Paradoxically, revascularization was markedly accelerated and neovascularization markedly reduced in mice maintained in prolonged hyperoxia (P7-P27) compared with mice recovering in room air. The extended use of 75% oxygen during the recovery period was associated with preservation of astrocytes and Müller cells in the avascular retina. The antiangiogenic effect of hyperoxia on retinal capillaries is strongly dependent on postnatal age. A protocol of continuous 75% supplemental oxygen accelerates recovery of inner retinal vasculature and prevents vitreous neovascularization, by a mechanism that may involve preservation of inner retinal glia.Investigative Ophthalmology & Visual Science 03/2002; 43(2):496-502. · 3.66 Impact Factor
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ABSTRACT: The inner vasculature of the retina develops as a spreading network, which is preceded by spindle-shaped cells. These cells are alleged to be vascular precursor cells (angioblasts). This study was designed to test whether such angioblasts exist in neonatal mouse retina. In situ hybridization and immunohistochemistry on mouse retinal wholemount preparations were used to visualize specific vascular cell types. In situ hybridization with an RNA probe against vascular endothelial growth factor receptor (VEGFR)-2 (a marker for endothelial cells and angioblasts) labeled the vascular network but failed to label the spindle-shaped cells in front of it. A probe against VEGFR1, a marker for endothelial cells only, revealed the same staining pattern. Pericytes, visualized with a probe against platelet-derived growth receptor (PDGFR)-beta, were spread over the entire vessel network, but not beyond it. However, in situ hybridization with a probe against PDGFRalpha (a marker for retinal astrocytes) labeled spindle-shaped cells preceding the vessel network. These observations imply that in the mouse retina the spindle-shaped cells preceding the forming vasculature are immature retinal astrocytes and not vascular precursor cells and that the primary vascular network in the retina develops by angiogenesis (budding from existing vessels) and not vasculogenesis (assembly of dispersed angioblasts).Investigative Ophthalmology & Visual Science 03/2002; 43(2):522-7. · 3.66 Impact Factor