Choriocapillaris changes in dry age-related macular degeneration and geographic atrophy: a review

Arya, Malvika; Sabrosa, Almyr S.; Duker, Jay S.; Waheed, Nadia K.

doi:10.1186/s40662-018-0118-x

Cited by 79 publications

(58 citation statements)

References 67 publications

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“…The presence of pachydrusen may result in some degree of RPE and/or photoreceptor dysfunction inducing choriocapillaris atrophy and arteriovenous shunting with resultant venous dilation. 22 In this study, the mean age was oldest in PCV and then PNV. The number of pachydrusen per eye was also higher in PCV and PNV.…”

Section: Discussionmentioning

confidence: 53%

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Choroidal morphology under pachydrusen

Baek

Lee

Chung

et al. 2018

Clinical Exper Ophthalmology

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Importance To reveal choroidal morphological profiles under pachydrusen. Background Drusen in pachychoroid disorders show certain differences from conventional drusen and are recently named as “pachydrusen.” This study analysed the specific choroidal morphology under pachydrusen. Design This study is a cross‐sectional case series. Participants Enrolled were 136 eyes with pachydrusen from 134 patients. Methods The presence of pachydrusen in fundus area covered by a 12 × 9 mm2 optical coherence tomography (OCT) image was accessed in eyes with pachychoroid‐related diseases or their fellow eyes using colour fundus photography and swept source OCT. Choroidal morphology under the pachydrusen was analysed using OCT B‐scans and en face images. Main Outcome Measures Choroidal thicknesses and topographical correlation between pachydrusen and pachyvessels. Results A total of 225 pachydrusen in 136 eyes were analysed. The mean number of pachydrusen was 1.65 ± 1.07 per eye. Most pachydrusen were located para‐ or perifoveally (37 subfoveal, 86 parafoveal and 102 perifoveal). The proportion of Haller's layer to total choroidal thickness was higher at the area of the pachydrusen compared to the subfovea (0.881 ± 0.081 vs 0.765 ± 0.111, P < 0.001). In multimodal image analysis, 90.1% of pachydrusen identified using fundus photography and OCT B‐scan were located at the area of a dilated Haller vessel (pachyvessel) seen on en face images. Conclusions and Relevance Choroidal morphology under the pachydrusen showed increased Haller's layer thickness with an attenuated choriocapillaris layer, which is the hallmark of pachychoroid definition. Topographically, their locations correlated with the underlying pachyvessel.

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Section: Discussionmentioning

confidence: 53%

“…On the other hand, pachydrusen may precede the choroidal changes. The presence of pachydrusen may result in some degree of RPE and/or photoreceptor dysfunction inducing choriocapillaris atrophy and arteriovenous shunting with resultant venous dilation …”

Section: Discussionmentioning

confidence: 99%

Choroidal morphology under pachydrusen

Baek

Lee

Chung

et al. 2018

Clinical Exper Ophthalmology

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“…A few laser-, mechanically-, and chemically-induced large animal models are available but not often used so far [20,21]. Finally, in AMD, not only the RPE is affected but also the composition of BM is changing [22] and the choroid is thinning [23]. Thus, the ageing of the BM and choriocapillaris, in addition to the ageing RPE and retina, should also be considered when performing transplantation experiments in AMD animal models.…”

Section: Rpe Replacements As Experimental Therapies In Amdmentioning

confidence: 99%

A Systematic Review on Transplantation Studies of the Retinal Pigment Epithelium in Animal Models

Koster

Wever

Wagstaff

et al. 2020

IJMS

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The retinal pigment epithelium (RPE) and the adjacent light-sensitive photoreceptors form a single functional unit lining the back of the eye. Both cell layers are essential for normal vision. RPE degeneration is usually followed by photoreceptor degeneration and vice versa. There are currently almost no effective therapies available for RPE disorders such as Stargardt disease, specific types of retinitis pigmentosa, and age-related macular degeneration. RPE replacement for these disorders, especially in later stages of the disease, may be one of the most promising future therapies. There is, however, no consensus regarding the optimal RPE source, delivery strategy, or the optimal experimental host in which to test RPE replacement therapy. Multiple RPE sources, delivery methods, and recipient animal models have been investigated, with variable results. So far, a systematic evaluation of the (variables influencing) efficacy of experimental RPE replacement parameters is lacking. Here we investigate the effect of RPE transplantation on vision and vision-based behavior in animal models of retinal degenerated diseases. In addition, we aim to explore the effect of RPE source used for transplantation, the method of intervention, and the animal model which is used. Methods: In this study, we systematically identified all publications concerning transplantation of RPE in experimental animal models targeting the improvement of vision (e.g., outcome measurements related to the morphology or function of the eye). A variety of characteristics, such as species, gender, and age of the animals but also cell type, number of cells, and other intervention characteristics were extracted from all studies. A risk of bias analysis was performed as well. Subsequently, all references describing one of the following outcomes were analyzed in depth in this systematic review: a-, b-, and c-wave amplitudes, vision-based, thickness analyses based on optical coherence tomography (OCT) data, and transplant survival based on scanning laser ophthalmoscopy (SLO) data. Meta-analyses were performed on the a-and b-wave amplitudes from electroretinography (ERG) data as well as data from vision-based behavioral assays. Results: original research articles met the inclusion criteria after two screening rounds. Overall, most studies were categorized as unclear regarding the risk of bias, because many experimental details were poorly reported. Twenty-three studies reporting one or more of the outcome measures of interest were eligible for either descriptive (thickness analyses based on OCT data; n = 2) or meta-analyses. RPE transplantation significantly increased ERG a-wave Int.(Hedges' g 1.181 (0.471-1.892), n = 6) and b-wave (Hedges' g 1.734 (1.295-2.172), n = 42) amplitudes and improved vision-based behavior (Hedges' g 1.018 (0.826-1.209), n = 96). Subgroup analyses revealed a significantly increased effect of the use of young and adolescent animals compared to adult animals. Moreover, transplanting more cells (in the range of 10 5 versus in the range o...

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“…Based on the extent of drusen, AMD can be roughly divided into three stages: early, intermediate and late stages. Late‐stage AMD is further categorized into two types: geographic atrophy and wet AMD, which refers to neovascular and abnormal blood vessel growth in the choriocapillaris and features in choroidal neovascularization (CNV) . Over‐proliferation of vasculature in wet AMD is causally linked to high level of vascular endothelial growth factor (VEGF) .…”

Section: Introductionmentioning

confidence: 75%

“…in the choriocapillaris and features in choroidal neovascularization (CNV). 5 Over-proliferation of vasculature in wet AMD is causally linked to high level of vascular endothelial growth factor (VEGF). 6 Well-presented evidences also indicate an intimate relationship between macrophages and AMD lesions, especially the initiation of CNV.…”

mentioning

confidence: 99%

MiR‐505 promotes M2 polarization in choroidal neovascularization model mice by targeting transmembrane protein 229B

Zhao

Lu²,

Liu

et al. 2019

Scand J Immunol

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We aimed to analyse the relative abundance of miR‐505 in age‐related macular degeneration (AMD) and elucidate its underlying mechanisms. Relative expression of miR‐505 was analysed by real‐time polymerase chain reaction (PCR). Macrophage polarization was characterized by measurement of molecular markers including Ym‐1, Arg‐1, TNF‐α and iNOS via both real‐time PCR and Western blot. Vascular endothelial growth factor (VEGF) content was determined by enzyme‐linked immunosorbent assay. Choroidal neovascularization (CNV) formation was evaluated by choroidal flat mount technique. The regulatory action of miR‐505‐5p on 3′UTR of Transmembrane Protein 229B (TMEM229B) was interrogated by luciferase reporter assay. miR‐505 was aberrantly upregulated in both AMD and laser‐induced choroidal neovascularization mouse model. Administration with miR‐505 specific inhibitor suppressed M2 polarization in CNV mice as indicated by decreasing both Ym‐1 and Arg‐1. Meanwhile, VEGF expression and CNV formation were greatly suppressed by miR‐505 inhibition as well. The similar phenotype was consolidated in Prostaglandin E2 (PGE2)‐stimulated bone marrow‐derived macrophages. At the molecular level, miR‐505‐5p directly targeted and negatively regulated TMEM229B expression, while forced ectopic expression of TMEM229B significantly rescued miR‐505‐imposed M2 polarization. Our data have uncovered the critical contribution of miR‐505 in AMD, which is predominantly mediated by downregulation of TMEM229B.

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Choriocapillaris changes in dry age-related macular degeneration and geographic atrophy: a review

Cited by 79 publications

References 67 publications

Choroidal morphology under pachydrusen

Choroidal morphology under pachydrusen

A Systematic Review on Transplantation Studies of the Retinal Pigment Epithelium in Animal Models

MiR‐505 promotes M2 polarization in choroidal neovascularization model mice by targeting transmembrane protein 229B

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