Optical Coherence Tomography and Histology of Age-Related Macular Degeneration Support Mitochondria as Reflectivity Sources

Litts, Katie M.; Zhang, Yuhua; Freund, K. Bailey; Curcio, Christine A.

doi:10.1097/iae.0000000000001946

Cited by 81 publications

(63 citation statements)

References 122 publications

(149 reference statements)

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“…Taking these intra-animal OCT comparisons together with our OCT to LM analysis, the 13-LGS B2 aligns to the outer one-third of the anatomical IS ellipsoid, which supports the model that mitochondria is a source of reflection in the IS. 45 , 46 However, when comparing the OCT to IF axial measurements, the B1 to B2 distance compared well to the total IS distance, which supported the IS/OS theory for B2 ( Supplementary Table S4 ). 5 The limitations of using these IF sets for structural comparisons are that antibody labeling of inner segment COX is being analyzed, rather than the IS structure itself (as in LM).…”

Section: Discussionmentioning

confidence: 56%

Assessment of Outer Retinal Remodeling in the Hibernating 13-Lined Ground Squirrel

Sajdak

Bell

Lewis

et al. 2018

Invest. Ophthalmol. Vis. Sci.

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PurposeWe examined outer retinal remodeling of the euthermic and torpid cone-dominant 13-lined ground squirrel (13-LGS) retina using optical coherence tomography (OCT) imaging and histology.MethodsRetinas and corneas of living 13-LGSs were imaged during euthermic and torpid physiological states using OCT. Retinal layer thickness was measured at the visual streak from registered and averaged vertical B-scans. Following OCT, some retinas were collected immediately for postmortem histologic comparison using light microscopy, immunofluorescence, or transmission electron microscopy.ResultsCompared to OCT images from euthermic retinae, OCT images of torpid retinae revealed significantly thicker inner and outer nuclear layers, as well as increases in the distances between outer retinal reflectivity bands 1 and 2, and bands 3 and 4. A significant decrease in the distance between bands 2 and 3 also was seen, alongside significant thinning of the choriocapillaris and choroid. OCT image quality was reduced in torpid eyes, partly due to significant thickening of the corneal stroma during this state.ConclusionsThe torpid retina of the hibernating 13-LGS undergoes structural changes that can be detected by OCT imaging. Comparisons between in vivo OCT and ex vivo histomorphometry may offer insight to the origin of hyperreflective OCT bands within the outer retina of the cone-dominant 13-LGS.

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Section: Discussionmentioning

confidence: 56%

Assessment of Outer Retinal Remodeling in the Hibernating 13-Lined Ground Squirrel

Sajdak

Bell

Lewis

et al. 2018

Invest. Ophthalmol. Vis. Sci.

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“…The EZ band was hypothesized to arise from the ellipsoid zone of the photoreceptor IS in humans. 7,71 The ellipsoid portions of the rod and cone IS are located at the same level or largely overlap in humans, nonhuman primates, 72 sheep, 50 and mice. 73 However, ultrastructural study in swine retinas have demonstrated that the ellipsoid portion of the cone IS lies at the level of the rod myoid, whereas the ellipsoid portion of the rod IS is located more externally, 74 which could lead to the observed ORB splitting on OCT. Because all tissues of the animals included in this study were Davidson fixed and paraffin embedded, no ultrastructural investigations could be performed to test this hypothesis.…”

Section: Discussionmentioning

confidence: 99%

Interspecies Variation of Outer Retina and Choriocapillaris Imaged With Optical Coherence Tomography

Soukup

Maloca

Altmann

et al. 2019

Invest. Ophthalmol. Vis. Sci.

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The purpose of this study is to assess with spectral-domain optical coherence tomography (OCT) the interspecies variation of outer retinal morphology and identification of choriocapillaris in four research animal species. METHODS. Spectralis HRAþOCT images acquired from locations dorsal, central, and ventral to the optic disc in healthy, anesthetized animals were evaluated by two independent readers. First, the number of OCT B-scans on which a choriocapillaris layer could clearly be identified was determined and quantified, and B-scans were correlated with histology. Second, B-scans demonstrating the highest number of discernable individual outer retinal bands (ORBs) were defined as ideal presentation and quantified. Interrater agreement was evaluated. RESULTS. Five-hundred seventy-four B-scans from 96 subjects were evaluated. The choriocapillaris layer was identified in 100.0% of minipig, 70.8% of rabbit, 75.4% of pigmented rat, 77.7% of albino rat, 56.5% of pigmented mouse, and 50.8% of albino mouse OCT scans. The percentage of ideal ORB presentation in B-scans was 11.7% in minipigs, 73.8% in rabbits, and 80.0%, 91.0%, 28.5%, and 62.5% in pigmented rats and mice and albino rats and mice, respectively. The interrater evaluation for both attributes showed substantial to perfect agreement in all species. CONCLUSIONS. The choriocapillaris is an easy and valid marker for identification of the outer retinal margin. ORB presentation likely varies due to differences in retinal anatomy and pigmentation between animal species and strains and between anatomic locations. Proper and consistent outer retinal margin and ORB identification are essential for research result reproducibility and translation.

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“…Because of excellent depth resolution, reflectivity can be localized to the subcellular level in OCT images [154]. It has been recently published highly reflective outer retinal tabulation prominent in late stage age-related macular degeneration [155]. Introduction of cellular-level imaging identifying the activity of single cells in living people [156,157] allowed more accurate pathology of the disease which was made complex by over-reliance on CFP and fundus auto fluorescence.…”

Section: Potential Use Of Non-genomic Tests and Modalities As Biomarkmentioning

confidence: 99%

Precision medicine for age-related macular degeneration: current developments and prospects

Biarnés

Vassilev

Nogoceke

et al. 2018

Expert Review of Precision Medicine and Drug Development

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Introduction: With the ageing population, diseases such as age-related macular degeneration (AMD) will become more prevalent. This will increase demand for provision of care on affected individuals, society and the healthcare system. To develop the best, individually tailored treatment for every patient, however, remains challenging. Areas covered: Recent identifications of interactions between environmental, lifestyle, genetic and non-genetic factors opened the potential for developing personalised approaches for the prevention and treatment of AMD. In this review, we will discuss the implications of these interactions for early to late disease stage conversion, for neovascularization and cell atrophy. We will put the findings of recent studies within the context of the regulatory framework requirements surrounding the development of personalised medicine approach to AMD. Expert Opinion: Precision medicine is now at a stage that it has its theoretical framework in place for the management of risk for patients with AMD requiring early diagnosis and timely treatment as several key components for such an approach are now clearly identified and are being applied to clinical developments successfully.

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Optical Coherence Tomography and Histology of Age-Related Macular Degeneration Support Mitochondria as Reflectivity Sources

Abstract: Our data support adoption of the ellipsoid zone nomenclature. Identifying subcellular signal sources will newly inform clinical.

Cited by 81 publications

References 122 publications

Assessment of Outer Retinal Remodeling in the Hibernating 13-Lined Ground Squirrel

Assessment of Outer Retinal Remodeling in the Hibernating 13-Lined Ground Squirrel

Interspecies Variation of Outer Retina and Choriocapillaris Imaged With Optical Coherence Tomography

Precision medicine for age-related macular degeneration: current developments and prospects

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