Early postnatal hyperoxia in mice leads to severe persistent vitreoretinopathy

Paul G. McMenamin, Rachel Kenny, Sjakon Tahija, Jeremiah Lim, Cecilia Naranjo Golborne, Xiangting Chen, Sheena Bouch, Foula Sozo, Bang Bui

Research output: Contribution to journalArticleResearchpeer-review

Abstract

PURPOSE. To describe a mouse model of hyperoxia-induced vitreoretinopathy that replicated some of the clinical and pathologic features encountered in infants with severe retinopathy of prematurity and congenital ocular conditions such as persistent hyperplastic primary vitreous. METHODS. Experimental mice (C57BL/6J) were exposed to 65% oxygen between postnatal days (P)0 to P7 and studied at P10, P14, and 3, 5, 8, 20, and 40 weeks. Controls were exposed to normoxic conditions. Fundus imaging and fluorescein angiography were performed at all time points, and spectral-domain optical coherence tomography (SD-OCT) and electroretinography were performed at 8-and 20-week time points. Eyes were processed for resin histology, frozen sections, and retinal whole mounts. Immunostaining was performed to visualize vasculature isolectin B4 (Ib4), collagen type IV, glial fibrillary acidic protein, and α-smooth muscle actin. RESULTS. Early exposure to hyperoxia resulted in bilateral vitreous hemorrhages at 3 weeks. From 5 weeks onward there were extensive zones of retinal degeneration, scarring or gliosis, retinal folding, and detachments caused by traction of α-smooth muscle actin-positive vitreous membranes. Tortuous retinal vessels, together with hyperplastic and persistence of hyaloid vessels are evident into adulthood. In the early stages (P10-3 weeks), branches from the tunica vasculosa lentis (TVL) supplied the marginal retina until retinal vessels were established. The peripheral retina remained poorly vascularized into adulthood. Electroretinography revealed 50% to 60% diminution in retinal function in adult mice that strongly correlated with vitreal changes identified using SD-OCT. CONCLUSIONS. This animal model displays a mixture of vitreoretinal pathologic changes that persist into adulthood. The model may prove valuable in experimental investigations of therapeutic approaches to blinding conditions caused by vitreous and retinal abnormalities.

Original languageEnglish
Pages (from-to)6513-6526
Number of pages14
JournalInvestigative Ophthalmology and Visual Science
Volume57
Issue number15
DOIs
Publication statusPublished - 1 Dec 2016

Keywords

  • Disease model
  • Hyaloid vasculature
  • Hyperoxia
  • Retinal vessels
  • Vitreoretinopathy

Cite this

McMenamin, Paul G. ; Kenny, Rachel ; Tahija, Sjakon ; Lim, Jeremiah ; Naranjo Golborne, Cecilia ; Chen, Xiangting ; Bouch, Sheena ; Sozo, Foula ; Bui, Bang. / Early postnatal hyperoxia in mice leads to severe persistent vitreoretinopathy. In: Investigative Ophthalmology and Visual Science. 2016 ; Vol. 57, No. 15. pp. 6513-6526.
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title = "Early postnatal hyperoxia in mice leads to severe persistent vitreoretinopathy",
abstract = "PURPOSE. To describe a mouse model of hyperoxia-induced vitreoretinopathy that replicated some of the clinical and pathologic features encountered in infants with severe retinopathy of prematurity and congenital ocular conditions such as persistent hyperplastic primary vitreous. METHODS. Experimental mice (C57BL/6J) were exposed to 65{\%} oxygen between postnatal days (P)0 to P7 and studied at P10, P14, and 3, 5, 8, 20, and 40 weeks. Controls were exposed to normoxic conditions. Fundus imaging and fluorescein angiography were performed at all time points, and spectral-domain optical coherence tomography (SD-OCT) and electroretinography were performed at 8-and 20-week time points. Eyes were processed for resin histology, frozen sections, and retinal whole mounts. Immunostaining was performed to visualize vasculature isolectin B4 (Ib4), collagen type IV, glial fibrillary acidic protein, and α-smooth muscle actin. RESULTS. Early exposure to hyperoxia resulted in bilateral vitreous hemorrhages at 3 weeks. From 5 weeks onward there were extensive zones of retinal degeneration, scarring or gliosis, retinal folding, and detachments caused by traction of α-smooth muscle actin-positive vitreous membranes. Tortuous retinal vessels, together with hyperplastic and persistence of hyaloid vessels are evident into adulthood. In the early stages (P10-3 weeks), branches from the tunica vasculosa lentis (TVL) supplied the marginal retina until retinal vessels were established. The peripheral retina remained poorly vascularized into adulthood. Electroretinography revealed 50{\%} to 60{\%} diminution in retinal function in adult mice that strongly correlated with vitreal changes identified using SD-OCT. CONCLUSIONS. This animal model displays a mixture of vitreoretinal pathologic changes that persist into adulthood. The model may prove valuable in experimental investigations of therapeutic approaches to blinding conditions caused by vitreous and retinal abnormalities.",
keywords = "Disease model, Hyaloid vasculature, Hyperoxia, Retinal vessels, Vitreoretinopathy",
author = "McMenamin, {Paul G.} and Rachel Kenny and Sjakon Tahija and Jeremiah Lim and {Naranjo Golborne}, Cecilia and Xiangting Chen and Sheena Bouch and Foula Sozo and Bang Bui",
year = "2016",
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McMenamin, PG, Kenny, R, Tahija, S, Lim, J, Naranjo Golborne, C, Chen, X, Bouch, S, Sozo, F & Bui, B 2016, 'Early postnatal hyperoxia in mice leads to severe persistent vitreoretinopathy' Investigative Ophthalmology and Visual Science, vol. 57, no. 15, pp. 6513-6526. https://doi.org/10.1167/iovs.16-19928

Early postnatal hyperoxia in mice leads to severe persistent vitreoretinopathy. / McMenamin, Paul G.; Kenny, Rachel; Tahija, Sjakon; Lim, Jeremiah; Naranjo Golborne, Cecilia; Chen, Xiangting; Bouch, Sheena; Sozo, Foula; Bui, Bang.

In: Investigative Ophthalmology and Visual Science, Vol. 57, No. 15, 01.12.2016, p. 6513-6526.

Research output: Contribution to journalArticleResearchpeer-review

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T1 - Early postnatal hyperoxia in mice leads to severe persistent vitreoretinopathy

AU - McMenamin, Paul G.

AU - Kenny, Rachel

AU - Tahija, Sjakon

AU - Lim, Jeremiah

AU - Naranjo Golborne, Cecilia

AU - Chen, Xiangting

AU - Bouch, Sheena

AU - Sozo, Foula

AU - Bui, Bang

PY - 2016/12/1

Y1 - 2016/12/1

N2 - PURPOSE. To describe a mouse model of hyperoxia-induced vitreoretinopathy that replicated some of the clinical and pathologic features encountered in infants with severe retinopathy of prematurity and congenital ocular conditions such as persistent hyperplastic primary vitreous. METHODS. Experimental mice (C57BL/6J) were exposed to 65% oxygen between postnatal days (P)0 to P7 and studied at P10, P14, and 3, 5, 8, 20, and 40 weeks. Controls were exposed to normoxic conditions. Fundus imaging and fluorescein angiography were performed at all time points, and spectral-domain optical coherence tomography (SD-OCT) and electroretinography were performed at 8-and 20-week time points. Eyes were processed for resin histology, frozen sections, and retinal whole mounts. Immunostaining was performed to visualize vasculature isolectin B4 (Ib4), collagen type IV, glial fibrillary acidic protein, and α-smooth muscle actin. RESULTS. Early exposure to hyperoxia resulted in bilateral vitreous hemorrhages at 3 weeks. From 5 weeks onward there were extensive zones of retinal degeneration, scarring or gliosis, retinal folding, and detachments caused by traction of α-smooth muscle actin-positive vitreous membranes. Tortuous retinal vessels, together with hyperplastic and persistence of hyaloid vessels are evident into adulthood. In the early stages (P10-3 weeks), branches from the tunica vasculosa lentis (TVL) supplied the marginal retina until retinal vessels were established. The peripheral retina remained poorly vascularized into adulthood. Electroretinography revealed 50% to 60% diminution in retinal function in adult mice that strongly correlated with vitreal changes identified using SD-OCT. CONCLUSIONS. This animal model displays a mixture of vitreoretinal pathologic changes that persist into adulthood. The model may prove valuable in experimental investigations of therapeutic approaches to blinding conditions caused by vitreous and retinal abnormalities.

AB - PURPOSE. To describe a mouse model of hyperoxia-induced vitreoretinopathy that replicated some of the clinical and pathologic features encountered in infants with severe retinopathy of prematurity and congenital ocular conditions such as persistent hyperplastic primary vitreous. METHODS. Experimental mice (C57BL/6J) were exposed to 65% oxygen between postnatal days (P)0 to P7 and studied at P10, P14, and 3, 5, 8, 20, and 40 weeks. Controls were exposed to normoxic conditions. Fundus imaging and fluorescein angiography were performed at all time points, and spectral-domain optical coherence tomography (SD-OCT) and electroretinography were performed at 8-and 20-week time points. Eyes were processed for resin histology, frozen sections, and retinal whole mounts. Immunostaining was performed to visualize vasculature isolectin B4 (Ib4), collagen type IV, glial fibrillary acidic protein, and α-smooth muscle actin. RESULTS. Early exposure to hyperoxia resulted in bilateral vitreous hemorrhages at 3 weeks. From 5 weeks onward there were extensive zones of retinal degeneration, scarring or gliosis, retinal folding, and detachments caused by traction of α-smooth muscle actin-positive vitreous membranes. Tortuous retinal vessels, together with hyperplastic and persistence of hyaloid vessels are evident into adulthood. In the early stages (P10-3 weeks), branches from the tunica vasculosa lentis (TVL) supplied the marginal retina until retinal vessels were established. The peripheral retina remained poorly vascularized into adulthood. Electroretinography revealed 50% to 60% diminution in retinal function in adult mice that strongly correlated with vitreal changes identified using SD-OCT. CONCLUSIONS. This animal model displays a mixture of vitreoretinal pathologic changes that persist into adulthood. The model may prove valuable in experimental investigations of therapeutic approaches to blinding conditions caused by vitreous and retinal abnormalities.

KW - Disease model

KW - Hyaloid vasculature

KW - Hyperoxia

KW - Retinal vessels

KW - Vitreoretinopathy

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U2 - 10.1167/iovs.16-19928

DO - 10.1167/iovs.16-19928

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