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...
Saved in:
| Main Authors: | , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2020-01-01
|
| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0226840&type=printable |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850204106823565312 |
|---|---|
| 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 |
| collection | DOAJ |
| 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 |
| id | doaj-art-d2e55ae9cde34035a82fb7d7686e1036 |
| institution | OA Journals |
| issn | 1932-6203 |
| language | English |
| publishDate | 2020-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-d2e55ae9cde34035a82fb7d7686e10362025-08-20T02:11:21ZengPublic Library of Science (PLoS)PLoS ONE1932-62032020-01-01151e022684010.1371/journal.pone.0226840Novel imaging biomarkers for mapping the impact of mild mitochondrial uncoupling in the outer retina in vivo.Bruce A BerkowitzHailey K OldsCollin RichardsJoydip JoyTilman RosalesRobert H PodolskyKaren Lins ChildersW Brad HubbardPatrick G SullivanShasha GaoYichao LiHaohua QianRobin Roberts<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.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0226840&type=printable |
| spellingShingle | 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. PLoS ONE |
| title | 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_short | 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 |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0226840&type=printable |
| work_keys_str_mv | AT bruceaberkowitz novelimagingbiomarkersformappingtheimpactofmildmitochondrialuncouplingintheouterretinainvivo AT haileykolds novelimagingbiomarkersformappingtheimpactofmildmitochondrialuncouplingintheouterretinainvivo AT collinrichards novelimagingbiomarkersformappingtheimpactofmildmitochondrialuncouplingintheouterretinainvivo AT joydipjoy novelimagingbiomarkersformappingtheimpactofmildmitochondrialuncouplingintheouterretinainvivo AT tilmanrosales novelimagingbiomarkersformappingtheimpactofmildmitochondrialuncouplingintheouterretinainvivo AT roberthpodolsky novelimagingbiomarkersformappingtheimpactofmildmitochondrialuncouplingintheouterretinainvivo AT karenlinschilders novelimagingbiomarkersformappingtheimpactofmildmitochondrialuncouplingintheouterretinainvivo AT wbradhubbard novelimagingbiomarkersformappingtheimpactofmildmitochondrialuncouplingintheouterretinainvivo AT patrickgsullivan novelimagingbiomarkersformappingtheimpactofmildmitochondrialuncouplingintheouterretinainvivo AT shashagao novelimagingbiomarkersformappingtheimpactofmildmitochondrialuncouplingintheouterretinainvivo AT yichaoli novelimagingbiomarkersformappingtheimpactofmildmitochondrialuncouplingintheouterretinainvivo AT haohuaqian novelimagingbiomarkersformappingtheimpactofmildmitochondrialuncouplingintheouterretinainvivo AT robinroberts novelimagingbiomarkersformappingtheimpactofmildmitochondrialuncouplingintheouterretinainvivo |