Neuronal and glial cell changes are determined by retinal vascularization in retinopathy of prematurity

Authors

  • Laura E. Downie,

    1. Department of Anatomy and Cell Biology, The University of Melbourne, Parkville, Victoria, Australia 3010
    2. Department of Optometry and Vision Sciences, The University of Melbourne, Parkville, Victoria, Australia 3010
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  • Michael J. Pianta,

    1. Department of Optometry and Vision Sciences, The University of Melbourne, Parkville, Victoria, Australia 3010
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  • Algis J. Vingrys,

    1. Department of Optometry and Vision Sciences, The University of Melbourne, Parkville, Victoria, Australia 3010
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  • Jennifer L. Wilkinson-Berka,

    1. Department of Immunology, Monash University, Prahran, Victoria, Australia 3040
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  • Erica L. Fletcher

    Corresponding author
    1. Department of Anatomy and Cell Biology, The University of Melbourne, Parkville, Victoria, Australia 3010
    • Department of Anatomy and Cell Biology, The University of Melbourne, Grattan St., Parkville, Victoria, Australia 3010
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Abstract

We have characterized the vascular, neuronal, and glial changes in oxygen-induced retinopathy, a model of retinopathy of prematurity (ROP). Newborn Sprague-Dawley rats were exposed to either 80% ± 2% oxygen to postnatal day P11 and then room air until P18 (ROP) or room air for the entire duration (controls). Retinal structure was examined under the light microscope and following postembedding immunocytochemistry in central, midperipheral, and peripheral regions. Müller cells were evaluated immunocytochemically with glial fibrillary acidic protein. The extent of vascularization was established histologically. ROP caused significant thinning of the inner cellular and plexiform layers, which became more pronounced in the peripheral inner nuclear layer of ROP animals (11.3% loss vs. 25.4% loss). Amacrine cell amino acid levels were particularly vulnerable in the peripheral retina; bipolar cells showed similar but less prominent changes. Müller cells had elevated glutamine levels and were most gliotic in the periphery. The vasculature extended to peripheral retinal regions at P18 in controls but not in ROP rats. The most striking pattern of change was evident in the midperipheral “transition zone” of ROP animals. Areas close to blood vessels showed neurochemical properties that were similar to those of the central retina, indicating a local protective effect of the inner retinal blood supply. We find that ROP produces complex vascular, neural, and glial changes that relate to the proximity of inner retinal blood vessels. J. Comp. Neurol. 504:404–417, 2007. © 2007 Wiley-Liss, Inc.

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