June 2020
Volume 61, Issue 7
Free
ARVO Annual Meeting Abstract  |   June 2020
Novel Imaging Biomarkers for Mapping the Impact of Mild Mitochondrial Uncoupling in the Outer Retina In Vivo
Author Affiliations & Notes
  • Yichao Li
    Visual Function Core, National Eye Institute, Bethesda, Maryland, United States
  • Shasha Gao
    Ophthalmology, Zhengzhou University, China
    Visual Function Core, National Eye Institute, Bethesda, Maryland, United States
  • Bruce A Berkowitz
    Ophthalmology, Visual and Anatomical Sciences, Wayne State University School of Medicine, Michigan, United States
  • Hailey Olds
    Ophthalmology, Visual and Anatomical Sciences, Wayne State University School of Medicine, Michigan, United States
  • Collin Richards
    Ophthalmology, Visual and Anatomical Sciences, Wayne State University School of Medicine, Michigan, United States
  • Joydip Joy
    Ophthalmology, Visual and Anatomical Sciences, Wayne State University School of Medicine, Michigan, United States
  • Tilman Rosales
    Ophthalmology, Visual and Anatomical Sciences, Wayne State University School of Medicine, Michigan, United States
  • Robin Roberts
    Ophthalmology, Visual and Anatomical Sciences, Wayne State University School of Medicine, Michigan, United States
  • Robert Podolsky
    Beaumont Health, Beaumont Research Institute, Michigan, United States
  • Karen Childers
    Beaumont Health, Beaumont Research Institute, Michigan, United States
  • Brad Hubbard
    Spinal Cord and Brain Injury Research Center, University of Kentucky, Kentucky, United States
    Neuroscience, University of Kentucky, Kentucky, United States
  • Patrick Sullivan
    Spinal Cord and Brain Injury Research Center, University of Kentucky, Kentucky, United States
    Neuroscience, University of Kentucky, Kentucky, United States
  • Haohua Qian
    Visual Function Core, National Eye Institute, Bethesda, Maryland, United States
  • Footnotes
    Commercial Relationships   Yichao Li, None; Shasha Gao, None; Bruce Berkowitz, None; Hailey Olds, None; Collin Richards, None; Joydip Joy, None; Tilman Rosales, None; Robin Roberts, None; Robert Podolsky, None; Karen Childers, None; Brad Hubbard, None; Patrick Sullivan, None; Haohua Qian, None
  • Footnotes
    Support  RO1 EY026584; R01AG058171; KSCHIRT14-13A; 1I01BX003405; EY000503; EY000530; P30 EY04068
Investigative Ophthalmology & Visual Science June 2020, Vol.61, 2524. doi:
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      Yichao Li, Shasha Gao, Bruce A Berkowitz, Hailey Olds, Collin Richards, Joydip Joy, Tilman Rosales, Robin Roberts, Robert Podolsky, Karen Childers, Brad Hubbard, Patrick Sullivan, Haohua Qian; Novel Imaging Biomarkers for Mapping the Impact of Mild Mitochondrial Uncoupling in the Outer Retina In Vivo. Invest. Ophthalmol. Vis. Sci. 2020;61(7):2524.

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

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Abstract

Purpose : To test the hypothesis that imaging biomarkers are useful for evaluating in vivo rod photoreceptor cell responses to a mitochondrial protonophore.

Methods : Intraperitoneal injections of either the mitochondrial uncoupler 2,4 dinitrophenol (DNP) or saline were given to mice with either higher [129S6/eVTac (S6)] or lower [C57BL/6J (B6)] mitochondrial reserve capacities and were studied in dark or light. We measured: (i) the external limiting membrane – retinal pigment epithelium region thickness (ELM-RPE; OCT), which decreases substantially with upregulation of a pH-sensitive water removal co-transporter on the apical portion of the RPE, and (ii) the outer retina R1 (= 1/(spin lattice relaxation time (T1), an MRI parameter proportional to oxygen / free radical content.

Results : In darkness, baseline rod energy production and consumption are relatively high compared to that in light, and additional metabolic stimulation with DNP provoked thinning of the ELM-RPE region compared to saline injection in S6 mice; ELM-RPE thickness was unresponsive to DNP in B6 mice. Also, dark-adapted S6 mice given DNP showed a decrease in outer retina R1 values compared to saline injection in the inferior retina. In dark-adapted B6 mice, transretinal R1 values were unresponsive to DNP in superior and inferior regions. In light, with its relatively lower basal rod energy production and consumption, DNP caused ELM-RPE thinning in both S6 and B6 mice.

Conclusions : The present results raise the possibility of non-invasively evaluating the mouse rod mitochondrial energy ecosystem using new DNP-assisted OCT and MRI in vivo assays.

This is a 2020 ARVO Annual Meeting abstract.

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