Choroidal Vessel Wall: Hypercholesterolaemia-Induced Dysfunction and Potential Role of Statins

Sebastián, José; Corral, Juan José Salazar; Montañana, Rosa de Hoz; Collado, Beatriz Isabel Gallego; Sebastián, Ana Isabel Ramírez; Casado, Alberto Triviño

doi:10.5772/47794

Cited by 5 publications

(5 citation statements)

References 158 publications

(233 reference statements)

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“… 27 , 28 The PDGFB gene, which produces the pericyte growth factor PDGFB, is expressed in ECs to recruit pericyte and maintain pericyte ensheathment. 29 – 31 The EC-to-pericyte ratio is 1:1 in retinal capillary vessels and 6:1 in choriocapillaris, 32 , 33 and this difference in pericyte coverage of endothelium supports our finding that retinal ECs showed higher PDGFB expression than did choroidal ECs.…”

Section: Discussionsupporting

confidence: 78%

Molecular, Cellular, and Functional Heterogeneity of Retinal and Choroidal Endothelial Cells

Kim

Lim

Park

et al. 2023

Invest. Ophthalmol. Vis. Sci.

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Purpose To investigate the endothelial heterogeneity across distinct vascular beds in the inner and outer blood–retinal barriers. Methods We evaluated the molecular, cellular, and functional differences between primary human retinal endothelial cells (HRECs) and human choroidal endothelial cells (HCECs) in terms of angiogenic and vasculogenic properties, permeability, and transcytosis. Tube formation assay, cell migration assay, in vitro permeability assay, microfluidic sprouting assay, and transcriptome analysis were performed. Results HRECs showed higher proliferation and migration activity than did HCECs, whereas the tube formation ability was similar between HRECs and HCECs. Under angiogenic stimuli, HCECs displayed earlier sprouting angiogenesis, but the overall speed was faster and more stable in HRECs. HRECs expressed higher levels of adherens junctional proteins, whereas the tight junctional genes and transcytosis-related genes were more highly expressed in HCECs. Angiopoietin-2 was predominantly expressed in HRECs, but vascular endothelial growth factor (VEGF) receptors were more strongly expressed in HCECs. Platelet-derived growth factor subunit B (PDGFB) was more highly expressed in HRECs, which correlates to the lower degree of pericyte coverage in choroidal blood vessels. Conclusions Retinal and choroidal ECs showed significant cellular and molecular heterogeneities that correlated with their functional characteristics. Retinal ECs are vasculogenic with high migratory characteristics and faster angiogenic sprouting, and they are more responsive to VEGF-induced permeability. In contrast, choroidal ECs express high levels of transcytosis genes, and they are vasculogenic, rather proliferative, adept in generating tip cells, and less responsive to VEGF-induced permeability.

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Section: Discussionsupporting

confidence: 78%

Molecular, Cellular, and Functional Heterogeneity of Retinal and Choroidal Endothelial Cells

Kim

Lim

Park

et al. 2023

Invest. Ophthalmol. Vis. Sci.

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“…3 A, 3 B). To determine whether the choroidal vasculature was also fluorescent, despite the lower number of VSMCs in their vessels, 25 we prepared a choroidal whole mount. We observed a characteristic pattern of choroidal vasculature whole mounts, with vessels appearing as circular openings surrounded by a fluorescent vessel wall ( Figs.…”

Section: Resultsmentioning

confidence: 99%

A Naturally Fluorescent Mgp Transgenic Mouse for Angiogenesis and Glaucoma Longitudinal Studies

Asokan

Mitra

Periasamy

et al. 2018

Invest. Ophthalmol. Vis. Sci.

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PurposeOur goal was to generate and characterize a new mouse model in which only angiogenesis- and glaucoma-relevant tissues would be naturally fluorescent. The Matrix Gla (MGP) gene is highly expressed in vascular smooth muscle cells (VSMC) and trabecular meshwork (TM). We sought to direct our Mgp-Cre.KI mouse recombinase to VSMC/TM cells to produce their longitudinal fluorescent profiles.MethodsHomozygous Mgp-Cre.KI mice were crossed with Ai9 homozygous reporter mice harboring a loxP-flanked STOP cassette preventing transcription of a DsRed fluorescent protein (tdTomato). The F1 double-heterozygous (Mgp-tdTomato) was examined by direct fluorescence, whole mount, histology, and fundus photography. Custom-made filters had 554/23 emission and 609/54 exciter nanometer wavelengths. Proof of concept of the model's usefulness was conducted by inducing guided imaging laser burns. Evaluation of a vessel's leakage and proliferation was followed by noninvasive angiography.ResultsThe Mgp-tdTomato mouse was viable, fertile, with normal IOP and ERG. Its phenotype exhibited red paws and snout (cartilage expression), which precluded genotyping. A fluorescent red ring was seen at the limbus and confirmed to be TM expression by histology. The entire retinal vasculature was red fluorescent (VSMC) and directly visualized by fundus photography. Laser burns on the Mgp-tdTomato allowed separation of leakiness and neovascularization evaluation parameters.ConclusionsThe availability of a transgenic mouse naturally fluorescent in glaucoma-relevant tissues and retinal vasculature brings the unique opportunity to study a wide spectrum of single and combined glaucomatous conditions in vivo. Moreover, the Mgp-tdTomato mouse provides a new tool to study mechanisms and therapeutics of retinal angiogenesis longitudinally.

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“…This suggests a possible role for ApoE in AMD pathology related to retinal lipid trafficking [ 53 ]. Although the HCL subjects were treated pharmacologically, we know from previous studies that normalization of lipid levels is not followed by complete recovery of normal retinal histology [ 22 ] and that the remaining retinal changes are mainly due to chronic sustained ischemia caused by alterations in retinal vessels, Bruch’s membrane, and the RPE [ 51 ]. These ischemic situations have a detrimental impact on the retinal neurons [ 51 ].…”

Section: Discussionmentioning

confidence: 99%

“…In fact, in previous work, we have shown that the presence of hard drusen (HD) in subjects without ApoE ɛ4 carriers and without a family history of AD causes a statistically significant reduction in choroidal thickness when compared with cognitively healthy subject carriers of ApoE ɛ4 with FH+ [ 21 ]. This reduction in choroidal thickness could mean a reduction in blood flow, which is also found in pathologies such as AMD, glaucoma, or diabetic retinopathy [ 22 , 23 , 24 ].…”

Section: Introductionmentioning

confidence: 99%

Characterization of Retinal Drusen in Subjects at High Genetic Risk of Developing Sporadic Alzheimer’s Disease: An Exploratory Analysis

López‐Cuenca

Salobrar‐García

Gil-Salgado

et al. 2022

JPM

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Having a family history (FH+) of Alzheimer’s disease (AD) and being a carrier of at least one ɛ4 allele of the ApoE gene are two of the main risk factors for the development of AD. AD and age-related macular degeneration (AMD) share one of the main risk factors, such as age, and characteristics including the presence of deposits (Aβ plaques in AD and drusen in AMD); however, the role of apolipoprotein E isoforms in both pathologies is controversial. We analyzed and characterized retinal drusen by optical coherence tomography (OCT) in subjects, classifying them by their AD FH (FH- or FH+) and their allelic characterization of ApoE ɛ4 (ApoE ɛ4- or ApoE ɛ4+) and considering cardiovascular risk factors (hypercholesterolemia, hypertension, and diabetes mellitus). In addition, we analyzed the choroidal thickness by OCT and the area of the foveal avascular zone with OCTA. We did not find a relationship between a family history of AD or any of the ApoE isoforms and the presence or absence of drusen. Subjects with drusen show choroidal thinning compared to patients without drusen, and thinning could trigger changes in choroidal perfusion that may give rise to the deposits that generate drusen.

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Choroidal Vessel Wall: Hypercholesterolaemia-Induced Dysfunction and Potential Role of Statins

Cited by 5 publications

References 158 publications

Molecular, Cellular, and Functional Heterogeneity of Retinal and Choroidal Endothelial Cells

Molecular, Cellular, and Functional Heterogeneity of Retinal and Choroidal Endothelial Cells

A Naturally Fluorescent Mgp Transgenic Mouse for Angiogenesis and Glaucoma Longitudinal Studies

Characterization of Retinal Drusen in Subjects at High Genetic Risk of Developing Sporadic Alzheimer’s Disease: An Exploratory Analysis

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