title: Retinal vessel pathologies in a rat model of periventricular leukomalacia: a new model for retinopathy of prematurity?
abstract: OBJECTIVE
  To characterize concurrent retinal vessel pathologies reminiscent to retinopathy of prematurity (ROP) in a rat model of periventricular leukomalacia (PVL), in order to identify uniform damage pathways in both organs, the eye and the brain.
  
  
  METHODS
  Ischemia was induced in Long Evans rat pups on postnatal day 6 (P6) with unilateral (left side) carotid ligation (UCL) followed by exposure to different oxygen concentrations. Four different groups were studied: group A, hypoxia/ischemia (UCL + 6% O2, 1 hour); group B, hyperoxia (80% O2, 24 hours); group C, hypoxia/ischemia + hyperoxia (UCL + 6% O2, 1 hour + 80% O2, 24 hours); and group D, normoxia. In groups A and C, both retinae were examined separately (left retina, group A [A-L], right retina, group A [A-R]; left retina, group C [C-L], right retina, group C [C-R]). Morphologic analysis of vessel development based on flatmounts and cryosections was performed at P11 and P21. Quantitative (q)PCR was performed at P7, P11, and P21 (VEGF-A164, HIF-1α, EpoR, TNFα, iNOS, BMP-9, and IGF-1).
  
  
  RESULTS
  On flatmounts, distinct retardation in deeper vascular plexus development was observed, most prominent in A-L and C-L. Retinae of groups A-L and C-L displayed reduced capillary-free zones and an increased number of branching points at P11. Quantitative PCR analysis showed significantly different expression profiles of IGF-1 in A-L and B compared with D over the time course of the experiment.
  
  
  CONCLUSIONS
  This is the first report on concurring damage to the retina that was evaluated in a rat model of white matter injury in the developing brain. The relatively mild damage to the retinal vessel system may represent the basis for a model of moderate forms of ROP and to study vascular remodeling.
authors.affiliation: Department of Ophthalmology, Justus-Liebig-University Giessen, Giessen, Germany.
authors.forename: Janina
authors.initials: J
authors.lastname: Steck
authors.affiliation: Department of Pediatrics, Philipps-University Marburg, Marburg, Germany.
authors.forename: Carolin
authors.initials: C
authors.lastname: Blueml
authors.affiliation: Department of Pediatrics, Philipps-University Marburg, Marburg, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Kampmann
authors.affiliation: Institute for Medical Biometry and Epidemiology, Philipps-University Marburg, Marburg, Germany.
authors.forename: Brandon
authors.initials: B
authors.lastname: Greene
authors.affiliation: Department of Pediatrics, Philipps-University Marburg, Marburg, Germany.
authors.forename: Rolf F
authors.initials: RF
authors.lastname: Maier
authors.affiliation: Department of Veterinary Anatomy, Justus-Liebig-University Giessen, Giessen, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Arnhold
authors.affiliation: Department of Pediatric Cardiology, Pediatric Heart Center, Justus-Liebig-University Giessen, Giessen, Germany.
authors.forename: Bettina
authors.initials: B
authors.lastname: Gerstner
authors.affiliation: Department of Ophthalmology, Justus-Liebig-University Giessen, Giessen, Germany.
authors.forename: Knut
authors.initials: K
authors.lastname: Stieger
authors.affiliation: Department of Ophthalmology, Justus-Liebig-University Giessen, Giessen, Germany.
authors.forename: Birgit
authors.initials: B
authors.lastname: Lorenz
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D004195:Disease Models, Animal; D005136:Eye Proteins / Q000096:biosynthesis / Q000235:genetics; D005786:Gene Expression Regulation; D007150:Immunohistochemistry; D007969:Leukomalacia, Periventricular / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D008856:Microscopy, Fluorescence; D012313:RNA / Q000235:genetics; D051381:Rats; D020318:Rats, Long-Evans; D012171:Retinal Vessels / Q000473:pathology*; D012178:Retinopathy of Prematurity / Q000235:genetics / Q000378:metabolism / Q000473:pathology*
chemical_list: D005136:Eye Proteins; D012313:RNA
keywords: angiogenesis; periventricular leukomalacia; retinal vasculature; retinopathy of prematurity; unilateral carotid ligation