Abstract
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.
Highlights
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
Our results indicate that HB magnitude represents a novel OCT biomarker of mitochondria respiration in human and mouse retina that is upstream of pH-triggered changes in external limiting membrane to retinal pigment epithelium (ELM-RPE) thickness
HB magnitude is measured as the absolute value of the peak amplitude from baseline, and width is measured as length between two half maximum points on each arm of the profile
Summary
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. HB magnitude and the external limiting membrane-retinal pigment epithelium (ELMRPE) thickness appear to be dependent on light exposure, which is known to alter photoreceptor mitochondria respiration. 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. Acidification triggers RPE to pump out water from the SRS and reduces the thickness of the external limiting membrane to retinal pigment epithelium (ELM-RPE)[21,22,23] This ELM-RPE change operates on a slow time scale and differs from the faster changes in OCT intensity and optical path elicited by light within a few seconds as measured by optoretinography (ORG)[8,24]. We noted that the HB magnitude is substantially decreased after dark-adaptation in mice[3,14,15], but its connection with changes in ELM-RPE thickness, an established biomarker of mitochondrial respiration (see above), is unclear
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