July 2019
Volume 60, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2019
Interphotoreceptor Retinoid-Binding Protein (IRBP) prevents myopia, independent of mouse genetic backgrounds
Author Affiliations & Notes
  • Shanu Markand
    Opthalmology, Emory University, Decatur, Georgia, United States
  • Somin Kim
    Opthalmology, Emory University, Decatur, Georgia, United States
  • Micah A Chrenek
    Opthalmology, Emory University, Decatur, Georgia, United States
  • Jeffrey H Boatright
    Opthalmology, Emory University, Decatur, Georgia, United States
    Atlanta VA Medical Center, Georgia, United States
  • John M Nickerson
    Opthalmology, Emory University, Decatur, Georgia, United States
  • Footnotes
    Commercial Relationships   Shanu Markand, None; Somin Kim, None; Micah Chrenek, None; Jeffrey Boatright, None; John Nickerson, None
  • Footnotes
    Support  NIH R01EY028450, R01EY021592, P30EY006360, F31EY028855, R01EY028859, T32EY07092, T32GM008490, the Abraham and Phyllis Katz Foundation, VA RR&D I01RX002806 and I21RX001924, VA RR&D C9246C (Atlanta Veterans Administration Center of Excellence in Vision and Neurocognitive Rehabilitation), and an unrestricted grant to the Department of Ophthalmology at Emory University from Research to Prevent Blindness, Inc.
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 2367. doi:https://doi.org/
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    • Get Citation

      Shanu Markand, Somin Kim, Micah A Chrenek, Jeffrey H Boatright, John M Nickerson; Interphotoreceptor Retinoid-Binding Protein (IRBP) prevents myopia, independent of mouse genetic backgrounds. Invest. Ophthalmol. Vis. Sci. 2019;60(9):2367. doi: https://doi.org/.

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

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Abstract

Purpose : IRBP plays a vital role in the visual cycle. Our group previously reported retinal degeneration (RD) and profound myopia in IRBP knockout (KO) on the C57BL6J background. The purpose of this study was to test whether IRBP KO on a DBA2 background would exhibit the same myopia as we observed on the C57BL6J background.

Methods : Both male and female and littermate controls were used. The genotype of mice was masked during the experiments. At P140-150, IRBP heterozygous (N=3) and IRBP KO (N=3) mice on the DBA2 background (N5F1) were subjected to whole-eye ocular biometry/SD-OCT, fundoscopy, ERG, body weight and body length examinations. Data are reported as mean ± SEM. Using an unpaired t-test with Welch's correction, a p-value < 0.05 was considered significant.

Results : We observed that myopia driven by IRBP deficiency overrides background differences. Data analysis revealed a significant increase in the total axial length (TAL) in IRBP KO compared with IRBP+/- mice (3899 ± 44.24 mm in KO, 3675 ± 35.74 in IRBP+/-, p=0.018). The primary contributor to increased TAL was vitreous chamber depth (VCD) in the KO (VCD, 979 ± 59.28 mm in KO, 569 ± 35.74 in IRBP+/-, p=0.0128). Myopia was accompanied by a 30% decline in total retinal thickness (RT) in KO (148.5 ± 2.57 mm in KO, 213.3 ± 1.202 in IRBP+/-, p=0.0002). A significant 40% decline in the amplitudes of a- and b- waves under both scotopic and photopic conditions was observed in IRBP KO compared with IRBP+/-. No significant differences were observed in central corneal thickness, anterior chamber depth, and lens thickness. Body weight (30.9 ± 3.51 grams in KO, 33.9 ± 2.46 in IRBP+/-) and length (4.367 ± 0.185 cm in KO, 4.433 ± 0.2186 in IRBP+/-) remained unaltered.
At a similar age, IRBP KO on the C57BL6J background, showed similar phenotype with TAL, 3696 ± 22.37 mm , 3445 ± 9.957 in C57 WT, p=0.0004 ; VCD, 766 ± 25.75 mm in KO, 548 ± 50.57 in C57 WT, p=0.0150; and RT, 207 ± 8.35 mm in KO, 166 ± 5.833 in C57 WT, p=0.0104.

Conclusions : Our data support the hypothesis of a similar ocular phenotype of IRBP KO on both inbred DBA2 and C57BL6J backgrounds. This indicates that the role of IRBP in myopia and RD is independent of strains/background. This also suggests similar mechanisms are associated with IRBP function in determining the axial length and prevention of photoreceptor death.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.

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