Novel imaging biomarkers for mapping the impact of mild mitochondrial uncoupling in the outer retina in vivo
Autoři:
Bruce A. Berkowitz aff001; Hailey K. Olds aff001; Collin Richards aff001; Joydip Joy aff001; Tilman Rosales aff001; Robert H. Podolsky aff002; Karen Lins Childers aff002; W. Brad Hubbard aff003; Patrick G. Sullivan aff003; Shasha Gao aff006; Yichao Li aff006; Haohua Qian aff006; Robin Roberts aff001
Působiště autorů:
Department of Ophthalmology, Visual and Anatomical Sciences, Wayne State University School of Medicine, Detroit, MI, United States of America
aff001; Beaumont Research Institute, Beaumont Health, Royal Oak, MI, United States of America
aff002; Spinal Cord and Brain Injury Research Center, University of Kentucky, Lexington, KY, United States of America
aff003; Department of Neuroscience, University of Kentucky, Lexington, KY, United States of America
aff004; Lexington VA Health Care System, Lexington, KY, United States of America
aff005; Visual Function Core, National Eye Institute, National Institutes of Health, Bethesda, MD, United States of America
aff006; Department of Ophthalmology, First Affiliated Hospital, Zhengzhou University, Zhengzhou, China
aff007
Vyšlo v časopise:
PLoS ONE 15(1)
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.pone.0226840
Souhrn
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.
Klíčová slova:
Mitochondria – Biomarkers – Magnetic resonance imaging – Eyes – Tomography – In vivo imaging – Oxygen – Retina
Zdroje
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