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Prenatal Hypoxia Is Associated with Long-Term Retinal Dysfunction in Rats

BACKGROUND: Intra-uterine growth restriction (IUGR) has been associated with increased predisposition to age-related complications. We tested the hypothesis that rat offspring models of IUGR would exhibit exacerbated, age-related retinal dysfunction. METHODS: Female Sprague-Dawley rats (maintained a...

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Autores principales: Bourque, Stephane L., Kuny, Sharee, Reyes, Laura M., Davidge, Sandra T., Sauvé, Yves
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3627650/
https://www.ncbi.nlm.nih.gov/pubmed/23610595
http://dx.doi.org/10.1371/journal.pone.0061861
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author Bourque, Stephane L.
Kuny, Sharee
Reyes, Laura M.
Davidge, Sandra T.
Sauvé, Yves
author_facet Bourque, Stephane L.
Kuny, Sharee
Reyes, Laura M.
Davidge, Sandra T.
Sauvé, Yves
author_sort Bourque, Stephane L.
collection PubMed
description BACKGROUND: Intra-uterine growth restriction (IUGR) has been associated with increased predisposition to age-related complications. We tested the hypothesis that rat offspring models of IUGR would exhibit exacerbated, age-related retinal dysfunction. METHODS: Female Sprague-Dawley rats (maintained at 11.5% O(2) from gestational day 15 to 21 to induce IUGR) and control offspring (maintained at 21% O(2) throughout pregnancy) had retinal function assessed at 2 months (young) and 14 months of age (aged) with electroretinogram (ERG) recordings. Retinal anatomy was assessed by immunofluorescence. RESULTS: Deficits in rod-driven retina function were observed in aged IUGR offspring, as evidenced by reduced amplitudes of dark-adapted mixed a-wave V(max) (by 49.3%, P<0.01), b-wave V(max) (by 42.1%, P<0.001) and dark-adapted peak oscillatory potentials (by 42.3%, P<0.01). In contrast to the rod-driven defects specific to aged IUGR offspring, light adapted ERG recordings revealed cone defects in young animals, that were stationary until old age. At 2 months, IUGR offspring had amplitude reductions for both b-wave (V(max) by 46%, P<0.01) and peak oscillatory potential (V(max) by 38%, P<0.05). Finally, defects in cone-driven responses were further confirmed by reduced maximal photopic flicker amplitudes at 2 (by 42%, P<0.001) and 14 months (by 34%, P = 0.06) and critical flicker fusion frequencies at 14 months (Control: 42±1 Hz, IUGR: 35±2 Hz, P<0.05). These functional changes were not paralleled by anatomical losses in IUGR offspring retinas. CONCLUSIONS: These data support that the developing retina is sensitive to stressors, and that pathways governing cone- and rod-driven function differ in their susceptibilities. In the case of prenatal hypoxia, cone- and rod-driven dysfunction manifest at young and old ages, respectively. We must, therefore, take into account the specific impact that fetal programming might exert on age-related retinal dystrophies when considering related diagnoses and therapeutic applications.
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spelling pubmed-36276502013-04-22 Prenatal Hypoxia Is Associated with Long-Term Retinal Dysfunction in Rats Bourque, Stephane L. Kuny, Sharee Reyes, Laura M. Davidge, Sandra T. Sauvé, Yves PLoS One Research Article BACKGROUND: Intra-uterine growth restriction (IUGR) has been associated with increased predisposition to age-related complications. We tested the hypothesis that rat offspring models of IUGR would exhibit exacerbated, age-related retinal dysfunction. METHODS: Female Sprague-Dawley rats (maintained at 11.5% O(2) from gestational day 15 to 21 to induce IUGR) and control offspring (maintained at 21% O(2) throughout pregnancy) had retinal function assessed at 2 months (young) and 14 months of age (aged) with electroretinogram (ERG) recordings. Retinal anatomy was assessed by immunofluorescence. RESULTS: Deficits in rod-driven retina function were observed in aged IUGR offspring, as evidenced by reduced amplitudes of dark-adapted mixed a-wave V(max) (by 49.3%, P<0.01), b-wave V(max) (by 42.1%, P<0.001) and dark-adapted peak oscillatory potentials (by 42.3%, P<0.01). In contrast to the rod-driven defects specific to aged IUGR offspring, light adapted ERG recordings revealed cone defects in young animals, that were stationary until old age. At 2 months, IUGR offspring had amplitude reductions for both b-wave (V(max) by 46%, P<0.01) and peak oscillatory potential (V(max) by 38%, P<0.05). Finally, defects in cone-driven responses were further confirmed by reduced maximal photopic flicker amplitudes at 2 (by 42%, P<0.001) and 14 months (by 34%, P = 0.06) and critical flicker fusion frequencies at 14 months (Control: 42±1 Hz, IUGR: 35±2 Hz, P<0.05). These functional changes were not paralleled by anatomical losses in IUGR offspring retinas. CONCLUSIONS: These data support that the developing retina is sensitive to stressors, and that pathways governing cone- and rod-driven function differ in their susceptibilities. In the case of prenatal hypoxia, cone- and rod-driven dysfunction manifest at young and old ages, respectively. We must, therefore, take into account the specific impact that fetal programming might exert on age-related retinal dystrophies when considering related diagnoses and therapeutic applications. Public Library of Science 2013-04-16 /pmc/articles/PMC3627650/ /pubmed/23610595 http://dx.doi.org/10.1371/journal.pone.0061861 Text en © 2013 Bourque et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Bourque, Stephane L.
Kuny, Sharee
Reyes, Laura M.
Davidge, Sandra T.
Sauvé, Yves
Prenatal Hypoxia Is Associated with Long-Term Retinal Dysfunction in Rats
title Prenatal Hypoxia Is Associated with Long-Term Retinal Dysfunction in Rats
title_full Prenatal Hypoxia Is Associated with Long-Term Retinal Dysfunction in Rats
title_fullStr Prenatal Hypoxia Is Associated with Long-Term Retinal Dysfunction in Rats
title_full_unstemmed Prenatal Hypoxia Is Associated with Long-Term Retinal Dysfunction in Rats
title_short Prenatal Hypoxia Is Associated with Long-Term Retinal Dysfunction in Rats
title_sort prenatal hypoxia is associated with long-term retinal dysfunction in rats
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3627650/
https://www.ncbi.nlm.nih.gov/pubmed/23610595
http://dx.doi.org/10.1371/journal.pone.0061861
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