Exaggerated eye growth in IRBP-deficient mice in early development

Jeffrey Wisard, Amanda Faulkner, Micah A. Chrenek, Timothy Waxweiler, Weston Waxweiler, Christy Donmoyer, Gregory I Liou, Cheryl M. Craft, Gregor F. Schmid, Jeffrey H. Boatright, Machelle T. Pardue, John M. Nickerson

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Abstract

Purpose. Because interphotoreceptor retinoid-binding protein (IRBP) is expressed before being needed in its presumptive role in the visual cycle, we tested whether it controls eye growth during development. Methods. The eyes of congenic IRBP knockout (KO) and C57BL/6J wild-type (WT) mice ranging in age from postnatal day (P)2 to P440 were compared by histology, laser micrometry, cycloplegic photorefractions, and partial coherence interferometry. Results. The size and weight of IRBP KO mouse eyes were greater than those of the WT mouse, even before eye-opening. Excessive ocular enlargement started between P7 and P10, with KO retinal arc lengths becoming greater compared with WT from P10 through P30 (18%; P < 0.01). The outer nuclear layer (ONL) of KO retinas became 20% thinner between P12 to P25, and progressed to 38% thinner at P30. At P30, there were 30% fewer cones per vertical section in KO than in WT retinas. Bromodeoxyuridine (BrdU) labeling indicated the same number of retinal cells were born in KO and WT mice. A spike in apoptosis was observed in KO outer nuclear layer at P25. These changes in size were accompanied by a large decrease in hyperopic refractive error, which reached -4.56 ± 0.70 diopters (D) versus +9.98 ± 0.993 D (mean ± SD) in WT, by postnatal day 60 (P60). Conclusions. In addition to its role in the visual cycle, IRBP is needed for normal eye development. How IRBP mediates ocular development is unknown.

Original languageEnglish (US)
Pages (from-to)5804-5811
Number of pages8
JournalInvestigative Ophthalmology and Visual Science
Volume52
Issue number8
DOIs
StatePublished - Jul 1 2011

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Growth
Knockout Mice
Retina
Interferometry
Mydriatics
Refractive Errors
Bromodeoxyuridine
interstitial retinol-binding protein
Growth and Development
Histology
Lasers
Cell Count
Apoptosis
Weights and Measures

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

Cite this

Wisard, J., Faulkner, A., Chrenek, M. A., Waxweiler, T., Waxweiler, W., Donmoyer, C., ... Nickerson, J. M. (2011). Exaggerated eye growth in IRBP-deficient mice in early development. Investigative Ophthalmology and Visual Science, 52(8), 5804-5811. https://doi.org/10.1167/iovs.10-7129

Exaggerated eye growth in IRBP-deficient mice in early development. / Wisard, Jeffrey; Faulkner, Amanda; Chrenek, Micah A.; Waxweiler, Timothy; Waxweiler, Weston; Donmoyer, Christy; Liou, Gregory I; Craft, Cheryl M.; Schmid, Gregor F.; Boatright, Jeffrey H.; Pardue, Machelle T.; Nickerson, John M.

In: Investigative Ophthalmology and Visual Science, Vol. 52, No. 8, 01.07.2011, p. 5804-5811.

Research output: Contribution to journalArticle

Wisard, J, Faulkner, A, Chrenek, MA, Waxweiler, T, Waxweiler, W, Donmoyer, C, Liou, GI, Craft, CM, Schmid, GF, Boatright, JH, Pardue, MT & Nickerson, JM 2011, 'Exaggerated eye growth in IRBP-deficient mice in early development', Investigative Ophthalmology and Visual Science, vol. 52, no. 8, pp. 5804-5811. https://doi.org/10.1167/iovs.10-7129
Wisard J, Faulkner A, Chrenek MA, Waxweiler T, Waxweiler W, Donmoyer C et al. Exaggerated eye growth in IRBP-deficient mice in early development. Investigative Ophthalmology and Visual Science. 2011 Jul 1;52(8):5804-5811. https://doi.org/10.1167/iovs.10-7129
Wisard, Jeffrey ; Faulkner, Amanda ; Chrenek, Micah A. ; Waxweiler, Timothy ; Waxweiler, Weston ; Donmoyer, Christy ; Liou, Gregory I ; Craft, Cheryl M. ; Schmid, Gregor F. ; Boatright, Jeffrey H. ; Pardue, Machelle T. ; Nickerson, John M. / Exaggerated eye growth in IRBP-deficient mice in early development. In: Investigative Ophthalmology and Visual Science. 2011 ; Vol. 52, No. 8. pp. 5804-5811.
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AU - Wisard, Jeffrey

AU - Faulkner, Amanda

AU - Chrenek, Micah A.

AU - Waxweiler, Timothy

AU - Waxweiler, Weston

AU - Donmoyer, Christy

AU - Liou, Gregory I

AU - Craft, Cheryl M.

AU - Schmid, Gregor F.

AU - Boatright, Jeffrey H.

AU - Pardue, Machelle T.

AU - Nickerson, John M.

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N2 - Purpose. Because interphotoreceptor retinoid-binding protein (IRBP) is expressed before being needed in its presumptive role in the visual cycle, we tested whether it controls eye growth during development. Methods. The eyes of congenic IRBP knockout (KO) and C57BL/6J wild-type (WT) mice ranging in age from postnatal day (P)2 to P440 were compared by histology, laser micrometry, cycloplegic photorefractions, and partial coherence interferometry. Results. The size and weight of IRBP KO mouse eyes were greater than those of the WT mouse, even before eye-opening. Excessive ocular enlargement started between P7 and P10, with KO retinal arc lengths becoming greater compared with WT from P10 through P30 (18%; P < 0.01). The outer nuclear layer (ONL) of KO retinas became 20% thinner between P12 to P25, and progressed to 38% thinner at P30. At P30, there were 30% fewer cones per vertical section in KO than in WT retinas. Bromodeoxyuridine (BrdU) labeling indicated the same number of retinal cells were born in KO and WT mice. A spike in apoptosis was observed in KO outer nuclear layer at P25. These changes in size were accompanied by a large decrease in hyperopic refractive error, which reached -4.56 ± 0.70 diopters (D) versus +9.98 ± 0.993 D (mean ± SD) in WT, by postnatal day 60 (P60). Conclusions. In addition to its role in the visual cycle, IRBP is needed for normal eye development. How IRBP mediates ocular development is unknown.

AB - Purpose. Because interphotoreceptor retinoid-binding protein (IRBP) is expressed before being needed in its presumptive role in the visual cycle, we tested whether it controls eye growth during development. Methods. The eyes of congenic IRBP knockout (KO) and C57BL/6J wild-type (WT) mice ranging in age from postnatal day (P)2 to P440 were compared by histology, laser micrometry, cycloplegic photorefractions, and partial coherence interferometry. Results. The size and weight of IRBP KO mouse eyes were greater than those of the WT mouse, even before eye-opening. Excessive ocular enlargement started between P7 and P10, with KO retinal arc lengths becoming greater compared with WT from P10 through P30 (18%; P < 0.01). The outer nuclear layer (ONL) of KO retinas became 20% thinner between P12 to P25, and progressed to 38% thinner at P30. At P30, there were 30% fewer cones per vertical section in KO than in WT retinas. Bromodeoxyuridine (BrdU) labeling indicated the same number of retinal cells were born in KO and WT mice. A spike in apoptosis was observed in KO outer nuclear layer at P25. These changes in size were accompanied by a large decrease in hyperopic refractive error, which reached -4.56 ± 0.70 diopters (D) versus +9.98 ± 0.993 D (mean ± SD) in WT, by postnatal day 60 (P60). Conclusions. In addition to its role in the visual cycle, IRBP is needed for normal eye development. How IRBP mediates ocular development is unknown.

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