April 2010
Volume 51, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2010
Abnormal Globe Shape and Severe Myopia in the IRBP Knockout Mouse
Author Affiliations & Notes
  • J. M. Nickerson
    Ophthalmology, Emory Univ Eye Center, Atlanta, Georgia
  • J. D. Wisard
    Ophthalmology, Emory University School of Medicine, Atlanta, Georgia
  • M. A. Chrenek
    Ophthalmology, Emory University, Atlanta, Georgia
  • C. B. Wright
    Ophthalmology, Emory University, Atlanta, Georgia
  • J. H. Boatright
    Ophthalmology, Emory University School of Med, Atlanta, Georgia
  • S. B. Jabbar
    Atlanta VA Medical Center, Rehab R & D Center, Atlanta, Georgia
  • A. E. Faulkner
    Medical Research,
    Atlanta VA Medical Center, Decatur, Georgia
  • G. F. Schmid
    Lens Design & Metrology, CIBA Vision Corporation, Duluth, Georgia
  • M. T. Pardue
    Emory Univ/Ophthal,
    Atlanta VA Medical Center, Decatur, Georgia
  • Footnotes
    Commercial Relationships  J.M. Nickerson, None; J.D. Wisard, None; M.A. Chrenek, None; C.B. Wright, None; J.H. Boatright, None; S.B. Jabbar, None; A.E. Faulkner, None; G.F. Schmid, G. Schmid, F; M.T. Pardue, None.
  • Footnotes
    Support  R01EY016470, R01EY014026, R01EY016435, P30EY006360, R24EY017045, T32EY007092; Research to Prevent Blindness, Inc., FFB, the Katz Foundation, FFS, & Rehab Res & Dev Ctr of Excellence, Atlanta VA Hosp.
Investigative Ophthalmology & Visual Science April 2010, Vol.51, 3669. doi:https://doi.org/
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      J. M. Nickerson, J. D. Wisard, M. A. Chrenek, C. B. Wright, J. H. Boatright, S. B. Jabbar, A. E. Faulkner, G. F. Schmid, M. T. Pardue; Abnormal Globe Shape and Severe Myopia in the IRBP Knockout Mouse. Invest. Ophthalmol. Vis. Sci. 2010;51(13):3669. doi: https://doi.org/.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: : IRBP is synthesized in photoreceptor cells, binds retinoids, and acts in the cone visual cycle. Here we sought retinal and ocular abnormalities in the IRBP knockout (KO) mouse and in heterozygous wild type/KO mice.

Methods: : Wild type C57BL/6 (WT), heterozygous WT/KO, and IRBP KO mice on the same C57BL/6 background were assessed at postnatal day 60 (P60). Histology (N>4), novel metrology with a laser noncontact micrometer (LM; N>13), photorefraction (N>10), and partial coherence interferometry (PCI; N> 9) were conducted. Statistics were ANOVA and a SNK post hoc test or t-test.

Results: : The anterior-posterior (A-P) length of the eye was different among WT, KO/WT, and KO mice. The A-P length trait was recessive: Mean eye length of KO mice was greater (3.55±0.041 mm; p<0.01) than either WT (3.23±0.069 mm) or WT/KO mice (3.22±0.039 mm) by LM. PCI measurements of axial length were 3.29±0.051 mm for WT and 3.50±0.035 mm for KO, confirming LM measurements. The equatorial axes, S-I and N-T, were also larger in KO mouse eyes (p<0.01). To confirm the ocular dimensions and to find changes in the retina, we performed histology on the three genotypes. The retinal thicknesses of WT and WT/KO were the same in all layers of the retina. Pilot analyses indicate no difference in the perimeter of WT and KO/WT retinas. However, the retina was thinned in KO mice by 40% (p<0.01), and retina circumference was longer by 20% compared to WT (p<0.01). Refractive measurements in P60 mice revealed significantly more myopia in IRBP KO mice compared to WT (-0.37 vs +9.7 diopters (D), respectively; p<0.01). These refractive differences are consistent with the elongated A-P axis and longer circumference of the retina in the KO. The IRBP WT/KO mice had an intermediate refractive power of +5.8D (p<0.01).

Conclusions: : Myopia and axial elongation with loss of the IRBP gene was unexpected. These abnormalities and death of retinal cells at weaning suggest a developmental role for IRBP. It is important that the retinal degeneration required loss of both copies of the IRBP gene. However, the deletion of only one copy of the gene resulted in a large change in refractive power, and the loss of two copies resulted in an even larger change, consistent with a semi-dominant mode of inheritance. IRBP has multiple functions in the eye.

Keywords: retinoids/retinoid binding proteins 
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