Retinal vessel pathologies in a rat model of periventricular leukomalacia: a new model for retinopathy of prematurity?

Abstract

PURPOSE:

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: Janina Steck, Carolin Blueml, Susanne Kampmann, Brandon Greene, Rolf F Maier, Stefan Arnhold, Bettina Gerstner, Knut Stieger, Birgit Lorenz
• Journal: Investigative ophthalmology & visual science (Invest Ophthalmol Vis Sci) Vol. 56 Issue 3 Pg. 1830-41 (Feb 19 2015) ISSN: 1552-5783 [Electronic] United States
• PMID: 25698709 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2015 The Association for Research in Vision and Ophthalmology, Inc.

Chemical References

• Eye Proteins
• RNA

Topics

• Animals
• Animals, Newborn
• Disease Models, Animal
• Eye Proteins (biosynthesis, genetics)
• Gene Expression Regulation
• Immunohistochemistry
• Leukomalacia, Periventricular (genetics, metabolism, pathology)
• Microscopy, Fluorescence
• RNA (genetics)
• Rats
• Rats, Long-Evans
• Retinal Vessels (pathology)
• Retinopathy of Prematurity (genetics, metabolism, pathology)