In vivo imaging of the inner retinal layer structure in mice after eye-opening using visible-light optical coherence tomography

Beckmann, Lisa; Cai, Zhen; Cole, James; Miller, D. A. B.; Liu, Mingna; Grannonico, Marta; Zhang, Xian; Ryu, Hyun Jung; Netland, Peter A.; Liu, Xiaorong

doi:10.1016/j.exer.2021.108756

Cited by 10 publications

(11 citation statements)

References 39 publications

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“…The retinal thickness measured in the healthy euglycemic mice matches a number of previous studies that reported cumulative retinal thickness from the inner limiting membrane to the RPE–photoreceptor complex. 39 , 68 , 69 We observed that the hyperglycemic mice have a thinner total retina than the euglycemic mice at all time points, a finding that supports previous reports. 39 , 59 We did not, however, observe a progressive thinning over the postnatal 4- to 20-week interval examined here, indicating that there does not seem to be a change in thickness despite approximately 16 weeks of hyperglycemia.…”

Section: Scientific Advancessupporting

confidence: 91%

In Vivo Capillary Structure and Blood Cell Flux in the Normal and Diabetic Mouse Eye

Dholakia

Guevara–Torres

Power

et al. 2022

Invest. Ophthalmol. Vis. Sci.

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Purpose To characterize the early structural and functional changes in the retinal microvasculature in response to hyperglycemia in the Ins2 Akita mouse. Methods A custom phase-contrast adaptive optics scanning light ophthalmoscope was used to image retinal capillaries of 9 Ins2 Akita positive (hyperglycemic) and 9 Ins2 Akita negative (euglycemic) mice from postnatal weeks 5 to 18. A 15 kHz point scan was used to image capillaries and measure red blood cell flux at biweekly intervals; measurements were performed manually. Retinal thickness and fundus photos were captured monthly using a commercial scanning laser ophthalmoscope/optical coherence tomography. Retinal thickness was calculated using a custom algorithm. Blood glucose and weight were tracked throughout the duration of the study. Results Elevated blood glucose (>250 mg/dL) was observed at 4 to 5 weeks of age in Ins2 Akita mice and remained elevated throughout the study, whereas euglycemic littermates maintained normal glucose levels. There was no significant difference in red blood cell flux, capillary anatomy, lumen diameter, or occurrence of stalled capillaries between hyperglycemic and euglycemic mice between postnatal weeks 5 and 18. Hyperglycemic mice had a thinner retina than euglycemic littermates ( p < 0.001), but retinal thickness did not change with duration of hyperglycemia despite glucose levels that were more than twice times normal. Conclusions In early stages of hyperglycemia, retinal microvasculature structure (lumen diameter, capillary anatomy) and function (red blood cell flux, capillary perfusion) were not impaired despite 3 months of chronically elevated blood glucose. These findings suggest that hyperglycemia alone for 3 months does not alter capillary structure or function in profoundly hyperglycemic mice.

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Section: Scientific Advancessupporting

confidence: 91%

In Vivo Capillary Structure and Blood Cell Flux in the Normal and Diabetic Mouse Eye

Dholakia

Guevara–Torres

Power

et al. 2022

Invest. Ophthalmol. Vis. Sci.

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“…Numerous animal studies have compared OCT against full-field light microscopy (LM) in the same subjects to assess or validate the ability of OCT to image 20 and measure 21 – 27 retinal layers. OCT has likewise been validated against confocal microscopy 28 , 29 and electron microscopy. 30 , 31 Yet, vigorous debate about the origins of some bands continues.…”

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confidence: 99%

“… 16 , 18 , 19 , 32 Most validation studies to date have used near-infrared OCT, with a depth resolution of 3.0 µm or coarser in vivo and as fine as 1.4 µm ex vivo, with LM, 20 – 26 , 33 , 34 with resolution limited by light diffraction. Previously, in vivo visible-light OCT was validated against confocal microscopy, 29 yet only bands that are commonly visualized by near-infrared OCT were assessed. Although valuable, the limited definition of both the in vivo OCT and ex vivo validation images in these prior studies precluded a comparison of OCT reflectivity against subcellular organization and organelle distributions.…”

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confidence: 99%

Subcellular Comparison of Visible-Light Optical Coherence Tomography and Electron Microscopy in the Mouse Outer Retina

Chauhan

Kho

Fitzgerald

et al. 2022

Invest. Ophthalmol. Vis. Sci.

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Purpose We employed in vivo, 1.0-µm axial resolution visible-light optical coherence tomography (OCT) and ex vivo electron microscopy (EM) to investigate three subcellular features in the mouse outer retina: reflectivity oscillations inner to band 1 (study 1); hyperreflective band 2, attributed to the ellipsoid zone or inner segment/outer segment (IS/OS) junction (study 2); and the hyperreflective retinal pigment epithelium (RPE) within band 4 (study 3). Methods Pigmented (C57BL/6J, n = 10) and albino (BALB/cJ, n = 3) mice were imaged in vivo. Enucleated eyes were processed for light and electron microscopy. Using well-accepted reference surfaces, we compared micrometer-scale axial reflectivity of visible-light OCT with subcellular organization, as revealed by 9449 annotated EM organelles and features across four pigmented eyes. Results In study 1, outer nuclear layer reflectivity peaks coincided with valleys in heterochromatin clump density (−0.34 ± 2.27 µm limits of agreement [LoA]). In study 2, band 2 depth on OCT and IS/OS junction depth on EM agreed (−0.57 ± 0.76 µm LoA), with both having similar distributions. In study 3, RPE electron dense organelle distribution did not agree with reflectivity in C57BL/6J mice, with OCT measures of RPE thickness exceeding those of EM (2.09 ± 0.89 µm LoA). Finally, RPE thickness increased with age in pigmented mice (slope = 0.056 µm/mo; P = 6.8 × 10 −7 ). Conclusions Visible-light OCT bands arise from subcellular organization, enabling new measurements in mice. Quantitative OCT–EM comparisons may be confounded by hydration level, particularly in the OS and RPE. Caution is warranted in generalizing results to other species.

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“…In addition, vis-OCT has greater contrast between retinal layers due to the higher backscattering properties of biological tissues in the visible light wavelength range [33]. Taking advantage of this improved resolution and increased contrast sensitivity, we developed vis-OCTF to analyze individual RGC axon bundles in vivo [34][35][36]40]. Thus far, we have demonstrated vis-OCTF in the mouse retina to visualize RGC axon bundles in vivo and validated these structures using confocal microscopy ex vivo [34].…”

Section: Rgc Axon Bundle Morphology As a New In Vivo Biomarker For Rg...mentioning

confidence: 99%

“…As a result, vis-OCT provides unique anatomical and functional imaging capabilities that facilitate RGC damage evaluation [33]. Recently, we developed vis-OCT fibergraphy (vis-OCTF) to visualize and quantify changes in individual RGC axon bundles in mice [34][35][36]. In this study, we applied vis-OCTF to track the changes of axon bundles following the ONC injury by quantifying four parameters: (1) lateral bundle width, (2) axial bundle height, (3) cross-sectional area, and (4) bundle shape.…”

Section: Introductionmentioning

confidence: 99%

Longitudinal analysis of retinal ganglion cell damage at individual axon bundle level in mice using visible-light optical coherence tomography fibergraphy

Grannonico

Miller

Gao

et al. 2022

Preprint

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We developed a new analytic tool based on visible-light optical coherence tomography fibergraphy (vis-OCTF) to longitudinally track individual axon bundle transformation following acute optic nerve crush injury (ONC) in mice. We analyzed four parameters: lateral bundle width, axial bundle height, cross-sectional area, and the shape of individual bundles. We showed that axon bundles became wider and thicker at 3-days post ONC. The bundle swelling at 3-days post-ONC has correlated with about 15% retinal ganglion cell (RGC) soma loss. At 6-days post-ONC, axon bundles showed a significant reduction in lateral width and cross-sectional area, followed by a reduction in bundle height at 9-days post-ONC. Bundle shrinking at 9-days post-ONC has correlated with about 68% RGC soma loss. Both experimental and simulated results suggested that the cross-sectional area of individual RGC axon bundles is more sensitive than the bundle width and height to indicate RGC soma loss. This study is the first to track and quantify individual RGC axon bundles in vivo following ONC injury and establish the correlation between the morphological changes of RGC axon bundles and RGC soma loss.

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In vivo imaging of the inner retinal layer structure in mice after eye-opening using visible-light optical coherence tomography

Cited by 10 publications

References 39 publications

In Vivo Capillary Structure and Blood Cell Flux in the Normal and Diabetic Mouse Eye

In Vivo Capillary Structure and Blood Cell Flux in the Normal and Diabetic Mouse Eye

Subcellular Comparison of Visible-Light Optical Coherence Tomography and Electron Microscopy in the Mouse Outer Retina

Longitudinal analysis of retinal ganglion cell damage at individual axon bundle level in mice using visible-light optical coherence tomography fibergraphy

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