Subretinal Mononuclear Cells in Coats' Disease Studied with RPE65 and CD163: Evidence for Histiocytoid Pigment Epithelial Cells

Barrantes, Paula Cortes; Yonekawa, Yoshihiro; Lad, Eleonora M.; Proia, Alan D.

doi:10.1016/j.ajo.2020.09.020

Cited by 11 publications

(8 citation statements)

References 35 publications

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“…To elucidate the molecular repertoire of RPE phenotypes corresponding to HRF, we obtained human donor eyes with and without AMD and performed immunohistochemistry. We used antibodies for retinoid- and immune-related proteins 26 ( Supplementary Table S1 ) and positive and negative controls in human tissues ( Supplementary Fig. S2 ).…”

Section: Methodsmentioning

confidence: 99%

Hyperreflective Foci, Optical Coherence Tomography Progression Indicators in Age-Related Macular Degeneration, Include Transdifferentiated Retinal Pigment Epithelium

Cao

Leong

Messinger

et al. 2021

Invest. Ophthalmol. Vis. Sci.

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Purpose By optical coherence tomography (OCT) imaging, hyperreflective foci (HRF) indicate progression risk for advanced age-related macular degeneration (AMD) and are in part attributable to ectopic retinal pigment epithelium (RPE). We hypothesized that ectopic RPE are molecularly distinct from in-layer cells and that their cross-retinal course follows Müller glia. Methods In clinical OCT (61 eyes, 44 patients with AMD, 79.4 ± 7.7 years; 29 female; follow-up = 4.7 ± 0.9 years), one HRF type, RPE plume (n = 129 in 4 morphologies), was reviewed. Twenty eyes of 20 donors characterized by ex vivo OCT were analyzed by histology (normal, 4; early/intermediate AMD, 7; geographic atrophy, 6; neovascular AMD, 3). Cryosections were stained with antibodies to retinoid (RPE65, CRALPB) and immune (CD68, CD163) markers. In published RPE cellular phenotypes, red immunoreactivity was assessed semiquantitatively by one observer (none, some cells, all cells). Results Plume morphology evolved over time and many resolved (40%). Trajectories of RPE plume and cellular debris paralleled Müller glia, including near atrophy borders. RPE corresponding to HRF lost immunoreactivity for retinoid markers and gained immunoreactivity for immune markers. Aberrant immunoreactivity appeared in individual in-layer RPE cells and extended to all abnormal phenotypes. Müller glia remained CRALBP positive. Plume cells approached and contacted retinal capillaries. Conclusions HRF are indicators not predictors of overall disease activity. Gain and loss of function starts with individual in-layer RPE cells and extends to all abnormal phenotypes. Evidence for RPE transdifferentiation, possibly due to ischemia, supports a proposed process of epithelial–mesenchyme transition. Data can propel new biomarkers and therapeutic strategies for AMD.

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Section: Methodsmentioning

confidence: 99%

Hyperreflective Foci, Optical Coherence Tomography Progression Indicators in Age-Related Macular Degeneration, Include Transdifferentiated Retinal Pigment Epithelium

Cao

Leong

Messinger

et al. 2021

Invest. Ophthalmol. Vis. Sci.

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“…Along with the change of fluorescence lifetime and an emission spectrum shift, cells may alter their properties and function. 65 A current immunohistochemistry investigation showed that abnormal RPE lose typical markers like the retinoid isomerohydrolase RPE65. On the other hand, they may gain properties of immune cells as shown by immunoreactivity for macrophage markers CD68 and CD163, 66, 41 Thus, HRF have been considered macrophages or microglia that phagocytosed RPE.…”

Section: Discussionmentioning

confidence: 83%

Progressive dysmorphia of retinal pigment epithelium in age related macular degeneration revealed by fluorescence lifetime imaging

Hammer

Jakob-Girbig

Schwanengel

et al. 2021

Preprint

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Purpose: To observe changes of the retinal pigment epithelium (RPE) on the transition from dysmorphia to atrophy in age related macular degeneration (AMD) by fluorescence lifetime imaging ophthalmoscopy (FLIO). Methods: Multimodal imaging including color fundus photography (CFP), optical coherence tomography (OCT), fundus autofluorescence (FAF) imaging, and FLIO was performed in 40 eyes of 37 patients with intermediate AMD and no evidence for geographic atrophy or macular neovascularization) (mean age: 74.2+/-7.0 years). Twenty-three eyes were followed for 28.3+/-18.3 months. Seven eyes had a second follow up after 46.6+/-9.0 months. Thickened RPE on OCT, hyperpigmentation on CFP, and migrated RPE, seen as hyperreflective foci (HRF) on OCT, were identified. Fluorescence lifetimes in two spectral channels (SSC: 500-560 nm, LSC: 560-720 nm) as well as emission spectrum intensity ratio (ESIR) of the lesions were measured by FLIO. Results: As hyperpigmented areas form and RPE migrates into the retina, FAF lifetimes lengthen and ESRI of RPE cells increase. Thickened RPE showed lifetimes of 256+/-49 ps (SSC) and 336+/-35 ps (LSC) and an ESIR of 0.552+/-0.079. For hyperpigmentation, these values were 317+/-68 ps (p<0.001), 377+/-56 ps (p<0.001), and 0.609+/-0.081 (p=0.001), respectively, and for HRF 337+/-79 ps (p<0.001), 414+/-50 ps (p<0.001), and 0.654+/-0.075 (p<0.001). Conclusions: In the process of RPE degeneration, comprising different steps of dysmorphia, hyperpigmentation, and migration, lengthening of FAF lifetimes and a hypsochromic shift of emission spectra can be observed by FLIO. Thus, FLIO might provide early biomarkers for AMD progression and contribute to our understanding of RPE pathology.

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“…IVTA’s efficacy in Coats disease may be explained by that, at a histopathological level, mononuclear macrophages were found to be abundantly present in the subretinal space in enucleated eyes. 21 Another potential advantage of IVTA over anti-VEGF agents is the decreased likelihood of a crunch effect described with the latter. 22 Increased intraocular VEGF levels have been shown in Coats disease and correlated with the extent of retinal detachment.…”

Section: Discussionmentioning

confidence: 99%

Adjunctive Intravitreal Triamcinolone Acetonide for Exudative Retinal Detachment in Coats Disease

Alsakran

Nowilaty

Ghazi

et al. 2021

Journal of VitreoRetinal Diseases

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Purpose: This work aims to assess the value of intravitreal triamcinolone acetonide (IVTA) as an adjunctive therapy in advanced Coats disease with exudative retinal detachment (ERD). Methods: A retrospective review was conducted of patients with Coats disease stage 3 or higher who received IVTA to decrease subretinal fluid (SRF), facilitate retinal ablative therapy, and avoid surgical drainage. Primary outcomes were SRF resolution and avoidance of surgical SRF drainage. Results: Seventeen eyes of 17 patients (mean, [SD] age, 3.9 [3.4] years) met the inclusion criteria. ERD configuration was bullous in 7 and shallow in 10 eyes. Following a single IVTA injection, ablative therapy was achieved after a mean (SD) of 2.1 (3.0) weeks. Complete SRF resolution was observed in 13 eyes (76.4%) after a mean of 1.3 IVTA injections and a mean of 2 (SD, 1.27) laser sessions, and none of these eyes required SRF drainage up to last follow-up (mean [SD], 50.5 [26.24] months). In 4 eyes with bullous ERD at presentation, SRF persisted ( P = .015) despite additional measures including surgical drainage. Final visual acuity ranged from 20/100 to no light perception. Cataract developed in 12 of the 17 eyes (70.5%). None developed an increase in intraocular pressure at final follow-up. Conclusions: IVTA injection can be a helpful adjunctive modality to address SRF in advanced Coats disease. It may obviate the need to surgically drain SRF to effectively treat the condition, particularly when the ERD is not highly bullous.

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Subretinal Mononuclear Cells in Coats' Disease Studied with RPE65 and CD163: Evidence for Histiocytoid Pigment Epithelial Cells

Cited by 11 publications

References 35 publications

Hyperreflective Foci, Optical Coherence Tomography Progression Indicators in Age-Related Macular Degeneration, Include Transdifferentiated Retinal Pigment Epithelium

Hyperreflective Foci, Optical Coherence Tomography Progression Indicators in Age-Related Macular Degeneration, Include Transdifferentiated Retinal Pigment Epithelium

Progressive dysmorphia of retinal pigment epithelium in age related macular degeneration revealed by fluorescence lifetime imaging

Adjunctive Intravitreal Triamcinolone Acetonide for Exudative Retinal Detachment in Coats Disease

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