| Autor: |
Gao S; Department of Ophthalmology, the First Affiliated Hospital, Zhengzhou University, Zhengzhou, China.; Visual Function Core, National Eye Institute, National Institutes of Health, Bethesda, MD, 20892, USA., Li Y; Visual Function Core, National Eye Institute, National Institutes of Health, Bethesda, MD, 20892, USA., Bissig D; Department of Neurology, University of California Davis, Sacramento, CA, USA., Cohen ED; Division of Biomedical Physics, Office of Science and Engineering Labs, Center for Devices and Radiological Health, Food and Drug Administration, Silver Spring, MD, USA., Podolsky RH; Beaumont Research Institute, Beaumont Health, Royal Oak, MI, 48073, USA., Childers KL; Beaumont Research Institute, Beaumont Health, Royal Oak, MI, 48073, USA., Vernon G; Visual Function Core, National Eye Institute, National Institutes of Health, Bethesda, MD, 20892, USA., Chen S; Visual Function Core, National Eye Institute, National Institutes of Health, Bethesda, MD, 20892, USA., Berkowitz BA; Department of Ophthalmology, Visual and Anatomical Sciences, Wayne State University School of Medicine, Detroit, MI, USA., Qian H; Visual Function Core, National Eye Institute, National Institutes of Health, Bethesda, MD, 20892, USA. Haohua.qian@nih.gov. |
| Abstrakt: |
Human and animal retinal optical coherence tomography (OCT) images show a hyporeflective band (HB) between the photoreceptor tip and retinal pigment epithelium layers whose mechanisms are unclear. In mice, HB magnitude and the external limiting membrane-retinal pigment epithelium (ELM-RPE) thickness appear to be dependent on light exposure, which is known to alter photoreceptor mitochondria respiration. Here, we test the hypothesis that these two OCT biomarkers are linked to metabolic activity of the retina. Acetazolamide, which acidifies the subretinal space, had no significant impact on HB magnitude but produced ELM-RPE thinning. Mitochondrial stimulation with 2,4-dinitrophenol reduced both HB magnitude and ELM-RPE thickness in parallel, and also reduced F-actin expression in the same retinal region, but without altering ERG responses. For mice strains with relatively lower (C57BL/6J) or higher (129S6/ev) rod mitochondrial efficacy, light-induced changes in HB magnitude and ELM-RPE thickness were correlated. Humans, analyzed from published data captured with a different protocol, showed a similar light-dark change pattern in HB magnitude as in the mice. Our results indicate that mitochondrial respiration underlies changes in HB magnitude upstream of the pH-sensitive ELM-RPE thickness response. These two distinct OCT biomarkers could be useful indices for non-invasively evaluating photoreceptor mitochondrial metabolic activity. |
