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Janina Steck, Carolin Blueml, Susanne Kampmann, Bettina Gerstner, Rolf Maier, Knut Stieger, Birgit Lorenz; Retinal pathology reminiscent of retinopathy of prematurity in a rat model for periventricular leucomalacia. Invest. Ophthalmol. Vis. Sci. 2013;54(15):5562.
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Alternating oxygen levels during delivery and supplemental oxygen therapies can cause enormous damage on the immature retinal vessel system of preterm infants. As a result, the occurrence of incomplete and pathological vascularization of the retina can lead to blindness in the worst case (retinopathy of prematurity, ROP). Likewise, the immature brain can develop periventricular leucomalacia (PVL), characterized by loss of oligodendrocytes in the periventricular area with subsequent white matter damage. Aim of this study was to examine damage to the retina and the brain in a model for PVL, in order to identify uniform damage pathways.
Ischemia was induced in P6 neonatal Long Evans Rats with unilateral carotid ligation (UCL), which have been exposed to different oxygen concentrations. In total, 4 different groups were examined: (1) hypoxia/ischemia (6%O2, 1h), (2) hyperoxia (80%O2, 24h), (3) hypoxia/ischemia + hyperoxia, (4) normoxia. Animals underwent in vivo angiographic examination of their retinae followed by post mortem morphological analysis of vessel development based on flatmounts and cryosections on days P11 and P21. Quantitative PCR was performed to investigate gene expression changes of angiogenic and inflammatory factors (VEGF, HIF1α, EPOR, TNFα, iNOS) on days P7, P11, and P21.
On flatmounts, distinct retardation in deeper vascular plexus development was observed, most prominent at P11 in eyes of groups 1 and 3. Alterations in the amount and diameter of large retinal vessels were observed as well as abnormal and uncoordinated/confused vessel growth in the retinal periphery. Eyes of animals from group 1 at P21 displayed the highest regression in superficial and deeper plexus vessels in retinal periphery. Quantitative gene expression analysis showed down regulation of angiogenic factors at P11 and P21.
This is the first report on concurring damage to the retina that was evaluated in a model of white matter injury in the neonatal brain. Considering results of standard models for ROP, there is relatively moderate damage on the retinal vessel system in our model, which is focused on the deeper vascular plexus. However, studying vessel growth in our rat model of PVL provides new information about deeper plexus development in the retina. Thus, it will help to correlate damage to the developing eye and brain in rodent models of neonatal brain injury.
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