Hyperreflective foci, OCT progression indicators in age-related macular degeneration, include transdifferentiated retinal pigment epithelium

Cao, Dongfeng; Leong, Belinda C.S.; Messinger, Jeffrey D.; Kar, Deepayan; Ach, Thomas; Yannuzzi, Lawrence A.; Freund, K. Bailey; Curcio, Christine A.

doi:10.1101/2021.04.26.21256056

Cited by 3 publications

(3 citation statements)

References 99 publications

(199 reference statements)

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“…For example, a higher concentration of melanolipofuscin is found in foveal RPE (Bermond et al, 2020). Other studies using optical coherence tomography suggest that hyperreflective foci (potentially associated with AMD progression) may be due to migrating RPE cells undergoing transdifferentiation (Ouyang et al, 2013;Cao et al, 2021), highlighting the three-dimensional nature of the disease.…”

Section: Discussionmentioning

confidence: 99%

Intercellular communication analysis of the human retinal pigment epithelial and choroidal cells predicts pathways associated with aging, cellular senescence and age-related macular degeneration

Dhirachaikulpanich

Lagger

Chatsirisupachai

et al. 2022

Front. Aging Neurosci.

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The retinal pigment epithelium (RPE) and the choroid are ocular tissues with fundamental roles in supporting neuroretinal function. The pathogenesis of age-related macular degeneration (AMD), a leading cause of irreversible blindness for which aging is the highest risk factor is closely linked with progressive impairment of various functions of these tissues. Cellular senescence, marked by cell cycle arrest and secretion of proinflammatory factors, is known to be associated with aging and has been proposed as a potential driver of AMD. Here, we investigated the role played by intercellular communication in the RPE/choroid within the context of aging, senescence and AMD. We inferred cell–cell interactions in the RPE/choroid by applying CellChat and scDiffCom on a publicly available scRNA-seq dataset from three human donors with and without AMD. We identified age-regulated ligand and receptor genes by using limma on a separate publicly available bulk microarray dataset providing RPE/choroid samples at multiple time points. Cellular senescence was investigated by assigning a score to each cell and each sample of these scRNA-seq and microarray datasets, respectively, based on the expression of key signature genes determined by a previous senescence meta-analysis. We identified VEGF-, BMP-and tenascin-mediated pathways supporting some of the strongest cell–cell interactions between RPE cells, fibroblasts and choroidal endothelial cells and as strong intercellular communication pathways related to both aging and senescence. Their signaling strength was enhanced between subpopulations of cells having high senescence scores. Predominant ligands of these pathways were upregulated with age whereas predominant receptors were downregulated. Globally, we also observed that cells from AMD samples presented slightly bigger senescence scores than normal cells and that the senescence score positively correlated with age in bulk samples (R = 0.26, value of p < 0.01). Hence, our analysis provides novel information on RPE/choroid intercellular communication that gives insights into the connection between aging, senescence and AMD.

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Section: Discussionmentioning

confidence: 99%

Intercellular communication analysis of the human retinal pigment epithelial and choroidal cells predicts pathways associated with aging, cellular senescence and age-related macular degeneration

Dhirachaikulpanich

Lagger

Chatsirisupachai

et al. 2022

Front. Aging Neurosci.

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“…It remains unclear whether macular hyperpigmentation in AMD represents a single or diverse group of histopathologic abnormalities. Hyperpigmentation in CFP has been attributed to the proliferation of RPE cells and increased concentration of melanin‐containing organelles (Cao et al, 2021).…”

Section: Introductionmentioning

confidence: 99%

Assessment of intraretinal hyperreflective foci using multimodal imaging in eyes with age‐related macular degeneration

Öncel

Corradetti

et al. 2023

Acta Ophthalmologica

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PurposeThis study aimed to investigate the correspondence between intraretinal hyperreflective foci (IHRF) identified on optical coherence tomography (OCT) B‐scans with hyperpigmentation on colour fundus photography (CFP) or hyperreflectivity on infrared reflectance (IR) images in eyes with age‐related macular degeneration (AMD).MethodsFlash CFP, IR images and OCT B‐scans obtained at the same visit were evaluated. Individual IHRF identified on OCT B‐scans were assessed for the qualitative presence or absence of a hypotransmission tail into the choroid. The corresponding IR image obtained at the time of OCT acquisition was analysed for the presence or absence of hyperreflectivity in this region. The IR images were manually registered to the CFP image, and CFP images were inspected for the presence or absence of hyperpigmentation at the location of IHRF.ResultsFrom 122 eyes, a total of 494 IHRF were evaluated. For the primary analysis of qualitative presence or absence of hyperpigmentation on CFP and hyperreflectivity on IR at the locations corresponding to IHRF on OCT, 301 (61.0%) of the IHRFs demonstrated evidence of hyperpigmentation on CFP, while only 115 (23.3%) showed evidence of hyperreflectivity on IR. The qualitative determination of the presence or absence of an abnormality on CFP or IR were significantly different (p < 0.0001). 327 (66.2%) of the IHRF showed hypotransmission, and 80.4% of these IHRF showed hyperpigmentation on CFP, though only 23.9% (p < 0.0001) demonstrated hyperreflectivity on IR.ConclusionsLess than two‐thirds of IHRF evident on OCT manifest as hyperpigmentation on colour photos, though IHRF with posterior shadowing are more likely to be evident as pigment. IR imaging appears to be even more poorly sensitive for visualizing IHRF.

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“…Nine eyes with unremarkable central retinas were used for this study. Detailed methods based on our previous studies (Cao et al, 2021;Chen et al, 2022;Anderson et al, 2023) are shown in Supplementary materials.…”

Section: Chromogenic Immunohistochemistry Of Macula-wide Cryosectionsmentioning

confidence: 99%

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Hyperreflective foci, OCT progression indicators in age-related macular degeneration, include transdifferentiated retinal pigment epithelium

Cited by 3 publications

References 99 publications

Intercellular communication analysis of the human retinal pigment epithelial and choroidal cells predicts pathways associated with aging, cellular senescence and age-related macular degeneration

Intercellular communication analysis of the human retinal pigment epithelial and choroidal cells predicts pathways associated with aging, cellular senescence and age-related macular degeneration

Assessment of intraretinal hyperreflective foci using multimodal imaging in eyes with age‐related macular degeneration

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