June 2015
Volume 56, Issue 7
Free
ARVO Annual Meeting Abstract  |   June 2015
Eye Elongation and Retinal Degeneration in the IRBP Knockout Mouse
Author Affiliations & Notes
  • Natecia Williams
    Ophthalmology, Emory University, Atlanta, GA
  • Shannon Getz
    Ophthalmology, Emory University, Atlanta, GA
  • Curran Sidhu
    Ophthalmology, Emory University, Atlanta, GA
  • Jeffrey H Boatright
    Ophthalmology, Emory University, Atlanta, GA
  • Machelle T Pardue
    Ophthalmology, Emory University, Atlanta, GA
  • P Michael Iuvone
    Ophthalmology, Emory University, Atlanta, GA
  • J M Nickerson
    Ophthalmology, Emory University, Atlanta, GA
  • Footnotes
    Commercial Relationships Natecia Williams, None; Shannon Getz, None; Curran Sidhu, None; Jeffrey Boatright, None; Machelle Pardue, None; P Iuvone, None; J Nickerson, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2015, Vol.56, 5847. doi:
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      Natecia Williams, Shannon Getz, Curran Sidhu, Jeffrey H Boatright, Machelle T Pardue, P Michael Iuvone, J M Nickerson; Eye Elongation and Retinal Degeneration in the IRBP Knockout Mouse. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):5847.

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

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Abstract

Purpose: Interphotoreceptor retinoid-binding protein (IRBP) is abundant in the subretinal space and binds retinoids and lipophilic molecules. Despite initial expression at embryonic day 12 (E12), the role of IRBP in eye development is unknown. Congenic IRBP-deficient mice (KO) show eye elongation starting at postnatal day 8 (P8), abnormal pruning indicated by reduced TUNEL-positive cell death in the inner nuclear layer by P12, increased TUNEL-positive cell death of photoreceptors at P23-P27, and profound myopia by P30 followed by slow retinal degeneration (RD) (Wisard et al. IOVS. 2011; 52:5804-11). Based on experimental myopia (Stone et al. PNAS 1989; 86:704-6), we propose KO mice will show a decrease in dopamine (DA) and the DA metabolite, 3,4-dihydroxyphenylacetic acid (DOPAC) and number of retinal dopaminergic cells (DA-cells) coinciding with abnormal eye elongation, abnormal pruning of inner retinal cells, and RD.

Methods: Using immunohistochemistry for tyrosine hydroxylase (TH) on retinal flat mounts, we counted the DA-cells in retinas of C57BL/6J (WT) and KO mice at P12-P30. HPLC was used to analyze the amounts of DA and DOPAC at P12-P30. t-tests for age-matched mice determined P-values.

Results: Although no difference was observed at P12, DOPAC levels in KO retinas increased by 64% at P23 (N=9 WT, 8 KO, P < 0.001) and 73% by P30 compared to WT mice (N=9 WT, 7 KO, P < 0.01). Similarly, KO retinal DA levels increased by 25% at P23 (N=9 WT, 8 KO, P < 0.01) and 21% at P30 compared to WT mice (N=9 WT, 7 KO, P < 0.05). The number of retinal TH+ cells was 28% greater in KO retinas compared to WT at P30 (N=4 WT, 4 KO, P<0.05).

Conclusions: Despite development of myopia, KO mice have increased levels of DA and DOPAC contrary to the expectation that high levels of DA should slow eye growth. The data would suggest that myopia observed in the KO mice is atypical to refractive myopia, independent of dopaminergic activity and visual input. The excess of TH+ cells in the KO retina may result from insufficient pruning of retinal DA-cells in the development of the KO inner retina. In addition, this high dopaminergic activity seems to be characteristic of KO retinas after P23, the age in which we begin to see a rise in cell death in the KO retina, which may suggest a role for DA or DA-cells in this RD.

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