Retinal vessel pathologies in a rat model of periventricular leucomalazia

Purpose Alternating oxygen levels during delivery and supplemental oxygen therapies can cause pathological vascularization of the retina (retinopathy of prematurity, ROP) and/or loss of oligodendrocytes in the periventricular area of the brain with subsequent white matter damage (periventricular leukomalacia (PVL). The aim of this study was to examine retinal vessel pathologies in the standard PVL rat model in order to identify uniform damage pathways. Methods Ischemia was induced in post natal day (P) 6 Long Evans rats with unilateral (left side) carotid ligation (UCL) and exposure to different oxygen concentrations. In total, four different groups were examined: (A) hypoxia/ischemia (UCL + 6% O2, 1 h), (B) hyperoxia (80%O2, 24 h), (C) hypoxia/ischemia + hyperoxia (UCL + 6% O2, 1 h + 80% O2, 24h), (D) normoxia. Morphological analysis of vessel development was performed at P11 and P21. Quantitative PCR was performed at P7, P11, and P21 (VEGF, HIF1a, EPOR, TNFa, iNOS and BMP‐9). Results Distinct retardation in deeper vascular plexus development was observed most prominent in left eyes of groups A and C. Diameters of big retinal arteries were significantly increased in central retinae at P21 and showed retardation in vascular remodeling. Left retinae of groups A and C at P11 displayed reduced capillary free zones (CFZ) and an increase in the number of branching points (BP). Quantitative gene expression analysis showed down regulation of angiogenic factors at P7. Conclusion 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. We observed mild damage to the vessel development and maturation, which is the basis for a model for moderate forms of ROP.