Novel imaging biomarkers for mapping the impact of mild mitochondrial uncoupling in the outer retina in vivo.
<h4>Purpose</h4>To test the hypothesis that imaging biomarkers are useful for evaluating in vivo rod photoreceptor cell responses to a mitochondrial protonophore.<h4>Methods</h4>Intraperitoneal injections of either the mitochondrial uncoupler 2,4 dinitrophenol (DNP) or saline...
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2020
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oai:doaj.org-article:d2e55ae9cde34035a82fb7d7686e10362021-12-02T20:05:47ZNovel imaging biomarkers for mapping the impact of mild mitochondrial uncoupling in the outer retina in vivo.1932-620310.1371/journal.pone.0226840https://doaj.org/article/d2e55ae9cde34035a82fb7d7686e10362020-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0226840https://doaj.org/toc/1932-6203<h4>Purpose</h4>To test the hypothesis that imaging biomarkers are useful for evaluating in vivo rod photoreceptor cell responses to a mitochondrial protonophore.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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.Bruce A BerkowitzHailey K OldsCollin RichardsJoydip JoyTilman RosalesRobert H PodolskyKaren Lins ChildersW Brad HubbardPatrick G SullivanShasha GaoYichao LiHaohua QianRobin RobertsPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 15, Iss 1, p e0226840 (2020) |
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Medicine R Science Q Bruce A Berkowitz Hailey K Olds Collin Richards Joydip Joy Tilman Rosales Robert H Podolsky Karen Lins Childers W Brad Hubbard Patrick G Sullivan Shasha Gao Yichao Li Haohua Qian Robin Roberts Novel imaging biomarkers for mapping the impact of mild mitochondrial uncoupling in the outer retina in vivo. |
| description |
<h4>Purpose</h4>To test the hypothesis that imaging biomarkers are useful for evaluating in vivo rod photoreceptor cell responses to a mitochondrial protonophore.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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. |
| format |
article |
| author |
Bruce A Berkowitz Hailey K Olds Collin Richards Joydip Joy Tilman Rosales Robert H Podolsky Karen Lins Childers W Brad Hubbard Patrick G Sullivan Shasha Gao Yichao Li Haohua Qian Robin Roberts |
| author_facet |
Bruce A Berkowitz Hailey K Olds Collin Richards Joydip Joy Tilman Rosales Robert H Podolsky Karen Lins Childers W Brad Hubbard Patrick G Sullivan Shasha Gao Yichao Li Haohua Qian Robin Roberts |
| author_sort |
Bruce A Berkowitz |
| title |
Novel imaging biomarkers for mapping the impact of mild mitochondrial uncoupling in the outer retina in vivo. |
| title_short |
Novel imaging biomarkers for mapping the impact of mild mitochondrial uncoupling in the outer retina in vivo. |
| title_full |
Novel imaging biomarkers for mapping the impact of mild mitochondrial uncoupling in the outer retina in vivo. |
| title_fullStr |
Novel imaging biomarkers for mapping the impact of mild mitochondrial uncoupling in the outer retina in vivo. |
| title_full_unstemmed |
Novel imaging biomarkers for mapping the impact of mild mitochondrial uncoupling in the outer retina in vivo. |
| title_sort |
novel imaging biomarkers for mapping the impact of mild mitochondrial uncoupling in the outer retina in vivo. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2020 |
| url |
https://doaj.org/article/d2e55ae9cde34035a82fb7d7686e1036 |
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