June 2017
Volume 58, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2017

Visual function following Nitisinone treatment in a mouse model of OCA-1B (Tyr c-h/c-h)
Author Affiliations & Notes
  • Ighovie Felix Onojafe
    OGVFB, NIH/NEI, Clinton, Maryland, United States
    POS, Priority One Services, Alexandria, Virginia, United States
  • Friedrich Kretschmer
    NNR-L, NEI/NIH, Bethesda, Maryland, United States
  • Jung-Woong Kim
    NNR-L, NEI/NIH, Bethesda, Maryland, United States
  • Kiyoharu Miyagishima
    OGVFB, NIH/NEI, Clinton, Maryland, United States
  • Congxiao Zhang
    OGVFB, NIH/NEI, Clinton, Maryland, United States
  • Haohua Qian
    NNR-L, NEI/NIH, Bethesda, Maryland, United States
  • Tudor C Badea
    NNR-L, NEI/NIH, Bethesda, Maryland, United States
  • Brian Patrick Brooks
    OGVFB, NIH/NEI, Clinton, Maryland, United States
  • Footnotes
    Commercial Relationships   Ighovie Onojafe, None; Friedrich Kretschmer, None; Jung-Woong Kim, None; Kiyoharu Miyagishima, None; Congxiao Zhang, None; Haohua Qian, None; Tudor Badea, None; Brian Brooks, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science June 2017, Vol.58, 5868. doi:
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      Ighovie Felix Onojafe, Friedrich Kretschmer, Jung-Woong Kim, Kiyoharu Miyagishima, Congxiao Zhang, Haohua Qian, Tudor C Badea, Brian Patrick Brooks;
      Visual function following Nitisinone treatment in a mouse model of OCA-1B (Tyr c-h/c-h). Invest. Ophthalmol. Vis. Sci. 2017;58(8):5868.

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

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Abstract

Purpose : Purpose:Oral nitisinone has been shown to increase fur and ocular pigmentation in a mouse model of oculocutanoeous albinism (OCA-1B) . OCA-1B is characterized by reduced melanin pigment in the hair, skin and eyes , decreased best-corrected visual acuity, transillumination and nystagmus. The purpose of this study is to determine the effect of this increase in pigmentation on visual function and retinal development.

Methods : Methods:Pregnant female Himalayan mice (OCA-1B) were treated daily with 8 mg/kg oral nitisinone (n=7) or vehicle (n=7) beginning at day 10 of pregnancy. Treatment continued after delivery and weaned pups additional month. Visual function was evaluated using Direct coupled electroretinogram (DC-ERG), Optokinetic response (OKR) and Optomotor response(OMR). Standard and DC-ERGs were performed on mice anesthetized with intraperitoneal injection of ketamine/xylazine. OMR was assessed by measuring reflexive head movements of unrestrained mice tracking a rotating virtual cylinder displaying a sine wave grating. OKR was performed on head fixed mice and eye movement recorded using an infrared reflective mirror, while displaying stimuli similar to the OMR. For retinal development; FACS/Rhodopsin test was used to determine cell population in the retina and specifically the rod population and Alexa Fluor Conjugated Cholera toxin B injection was used to show distribution of ganglion cell projections to the brain.

Results : Results:Treated Himalayan mice showed increase in fur and eye melanin pigment. While a- and b- waves of treated mice were close to wild type (WT) mice, the DC-ERG showed c-wave amplitude for untreated mice and WT was approx. 0.7 mV and 1.0 mV respectively. Intriguingly, this difference could be reversed by nitisinone treatment as the treated mice had close to 1.0 mV. The OMR/OKR showed that vision did not improve. The FACS/rhodopsin showed that there was 3-5 % increase in rods. All brain targets were correctly innervated with comparable numbers of ipsilateral and contralateral ganglion cell axons in the treated and untreated mice.

Conclusions : Conclusions:Prenatal treatment of Himalayan mice with nitisinone results in measurable changes in ERG responses and rod numbers of mice, but did not lead to a demonstrable change in visual behavior or axonal routing. These data will help in future studies in understanding the mechanism of RPE-mediated retinal development and visual function.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.

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