Maternal Vertical Transmission Provides a Mitochondrial Basis for ROP Susceptibility.
- 1Ophthalmic Research, Cole Eye Institute, Cleveland Clinic, Cleveland, Ohio, United States.
- 2Illinois Eye and Ear Infirmary, Department of Ophthalmology and Visual Sciences, University of Illinois Chicago, Chicago, Illinois, United States.
- 3Metabolomics & Cardiovascular Sciences, Cleveland Clinic Research, Cleveland Clinic, Cleveland, Ohio, United States.
Abstract
Purpose
The purpose of this study was to link strain-based susceptibility to mitochondria.Methods
Crosses between susceptible and protected strains of mice were analyzed for oxygen-induced retinopathy (OIR). Oxygen consumption and extracellular acidification of retina explants from individual strains were quantified. Expression and protein concentrations of key metabolic proteins were measured. Isotopic based metabolomics was used to measure transformations of glycolytic carbon.Results
A/J mice were protected from OIR compared to C57Bl/6 mice, having a 5-fold reduction in the ratio of vaso-obliteration (P = 1*10-5) and a 20-fold reduction in neovascularization (P = 0.002). Mapping among A/J, Balb/C, and C57Bl/6 mice showed a maternal inheritance pattern of protection that implicated mitochondria. A/J and C57Bl/6 mitochondrial functions showed a reduction in the basal respiration rates of A/J ex vivo retina (P = 4*10-9) and a two-fold reduction in the carboxyethyl pyrrole oxidative stress marker of A/J mice retinas with OIR (P = 0.007) compared with C57Bl/6 mice. Placed in hyperoxia, A/J mice retina demonstrated reduced levels of respiratory proteins, as well as expression of subunit IVi1 of cytochrome c oxidase in comparison to C57Bl/6 (P = 3*10-6). To support the hypothesis that a reduction in oxidative phosphorylation was protective, C57Bl/6 mice were injected with the mitochondrial uncoupler 2,4 dinitrophenylhydrazine (DNP) during the hyperoxia phase of OIR; DNP created reduced levels of vaso-obliteration (P = 1.5*10-5) and neovascularization (P = 8*10-6). Isotopic metabolomics demonstrated that A/J aortic endothelium increased glutamine (Gln) synthesis from glycolytic carbon in comparison to C57Bl/6 with upregulation of Hmox1 expression.Conclusions
Strain-specific susceptibility or protection may involve vertical maternal transmission.
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BibTeX
@article{fung2026maternal,
title = {{Maternal Vertical Transmission Provides a Mitochondrial Basis for ROP Susceptibility.}},
author = {Kevin Fung and George Hoppe and Andrew Benos and Demiana Hanna and Ke Jiang and Jonathan E Sears},
journal = {Investigative ophthalmology \& visual science},
year = {2026},
month = oct,
doi = {10.1167/iovs.67.12.78},
url = {https://europepmc.org/article/MED/42961307},
note = {CC BY},
}
RIS
TY - JOUR
TI - Maternal Vertical Transmission Provides a Mitochondrial Basis for ROP Susceptibility.
AU - Kevin Fung
AU - George Hoppe
AU - Andrew Benos
AU - Demiana Hanna
AU - Ke Jiang
AU - Jonathan E Sears
PY - 2026
DA - 2026/10/01
JO - Investigative ophthalmology & visual science
DO - 10.1167/iovs.67.12.78
UR - https://europepmc.org/article/MED/42961307
AB - Purpose The purpose of this study was to link strain-based susceptibility to mitochondria.Methods Crosses between susceptible and protected strains of mice were analyzed for oxygen-induced retinopathy (OIR). Oxygen consumption and extracellular acidification of retina explants from individual strains were quantified. Expression and protein concentrations of key metabolic proteins were measured. Isotopic based metabolomics was used to measure transformations of glycolytic carbon.Results A/J mice were protected from OIR compared to C57Bl/6 mice, having a 5-fold reduction in the ratio of vaso-obliteration (P = 1*10-5) and a 20-fold reduction in neovascularization (P = 0.002). Mapping among A/J, Balb/C, and C57Bl/6 mice showed a maternal inheritance pattern of protection that implicated mitochondria. A/J and C57Bl/6 mitochondrial functions showed a reduction in the basal respiration rates of A/J ex vivo retina (P = 4*10-9) and a two-fold reduction in the carboxyethyl pyrrole oxidative stress marker of A/J mice retinas with OIR (P = 0.007) compared with C57Bl/6 mice. Placed in hyperoxia, A/J mice retina demonstrated reduced levels of respiratory proteins, as well as expression of subunit IVi1 of cytochrome c oxidase in comparison to C57Bl/6 (P = 3*10-6). To support the hypothesis that a reduction in oxidative phosphorylation was protective, C57Bl/6 mice were injected with the mitochondrial uncoupler 2,4 dinitrophenylhydrazine (DNP) during the hyperoxia phase of OIR; DNP created reduced levels of vaso-obliteration (P = 1.5*10-5) and neovascularization (P = 8*10-6). Isotopic metabolomics demonstrated that A/J aortic endothelium increased glutamine (Gln) synthesis from glycolytic carbon in comparison to C57Bl/6 with upregulation of Hmox1 expression.Conclusions Strain-specific susceptibility or protection may involve vertical maternal transmission.
SN - 0146-0404
SN - 1552-5783
ER -