scholarly journals Concerted regulation of retinal pigment epithelium basement membrane and barrier function by angiocrine factors

2017 ◽  
Vol 8 (1) ◽  
Author(s):  
Ignacio Benedicto ◽  
Guillermo L. Lehmann ◽  
Michael Ginsberg ◽  
Daniel J. Nolan ◽  
Rohan Bareja ◽  
...  
Keyword(s):  
Retinal Pigment Epithelium ◽  
Basement Membrane ◽  
Barrier Function ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Angiocrine Factors

scholarly journals Pathogenic Effects of Mineralocorticoid Pathway Activation in Retinal Pigment Epithelium

2021 ◽  
Vol 22 (17) ◽  
pp. 9618
Author(s):  
Jérémie Canonica ◽  
Min Zhao ◽  
Tatiana Favez ◽  
Emmanuelle Gelizé ◽  
Laurent Jonet ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Retinal Pigment Epithelium ◽  
Barrier Function ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Retinal Diseases ◽  
Mesenchymal Transition ◽  
Rpe Cells ◽  
Pathway Activation ◽  
And Migration

Glucocorticoids are amongst the most used drugs to treat retinal diseases of various origins. Yet, the transcriptional regulations induced by glucocorticoid receptor (GR) and mineralocorticoid receptor (MR) activation in retinal pigment epithelium cells (RPE) that form the outer blood–retina barrier are unknown. Levels of endogenous corticoids, ligands for MR and GR, were measured in human ocular media. Human RPE cells derived from induced pluripotent stem cells (iRPE) were used to analyze the pan-transcriptional regulations induced by aldosterone—an MR-specific agonist, or cortisol or cortisol + RU486—a GR antagonist. The retinal phenotype of transgenic mice that overexpress the human MR (P1.hMR) was analyzed. In the human eye, the main ligand for GR and MR is cortisol. The iRPE cells express functional GR and MR. The subset of genes regulated by aldosterone and by cortisol + RU-486, and not by cortisol alone, mimics an imbalance toward MR activation. They are involved in extracellular matrix remodeling (CNN1, MGP, AMTN), epithelial–mesenchymal transition, RPE cell proliferation and migration (ITGB3, PLAUR and FOSL1) and immune balance (TNFSF18 and PTX3). The P1.hMR mice showed choroidal vasodilation, focal alteration of the RPE/choroid interface and migration of RPE cells together with RPE barrier function alteration, similar to human retinal diseases within the pachychoroid spectrum. RPE is a corticosteroid-sensitive epithelium. MR pathway activation in the RPE regulates genes involved in barrier function, extracellular matrix, neural regulation and epithelial differentiation, which could contribute to retinal pathology.

scholarly journals Three-dimensional shape analysis of peripapillary retinal pigment epithelium-basement membrane layer based on OCT radial images

2021 ◽  
Vol 10 (1) ◽  
pp. 453-464
Author(s):  
Junfei Tong ◽  
Pengfei Dong ◽  
Sachin Kedar ◽  
Deepta Ghate ◽  
Linxia Gu
Keyword(s):  
Mathematical Model ◽  
Retinal Pigment Epithelium ◽  
Basement Membrane ◽  
Optic Disc ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Three Dimensional ◽  
Full Potential ◽  
3D Morphology ◽  
Potential Index

Abstract The peripapillary retinal pigment epithelium-basement membrane (ppRPE/BM) layer angle was recently proposed as a potential index for estimating intracranial pressure noninvasively. However, the ppRPE/BM layer angle, measured from the optical coherence tomography (OCT) scans, varied across the radial directions of the optic disc. This made the ppRPE/BM layer angle difficult to be utilized in its full potential. In this study, we developed a mathematical model to quantify the ppRPE/BM layer angles across radial scans in relation to the ppRPE/BM 3D morphology in terms of its 3D angle and scanning tilt angles. Results showed that the variations of the ppRPE/BM layer angle across radial scans were well explained by its 3D angle and scanning tilt angles. The ppRPE/BM layer 3D angle was reversely fitted from the measured ppRPE/BM layer angles across radial directions with application to six eyes from four patients, who underwent medically necessary lumbar puncture. The fitted curve from our mathematical model matched well with the experimental measurements (R 2 > 0.9 in most cases). This further validated our mathematical model. The proposed model in this study has elucidated the variations of ppRPE/BM layer angle across 2D radial scans from the perspective of the ppRPE/BM layer 3D morphology. It is expected that the ppRPE/BM layer 3D angle developed in this study could be further exploited as a new biomarker for the optic disc.

scholarly journals Basement membrane stimulates the polarized distribution of integrins but not the Na,K-ATPase in the retinal pigment epithelium.

1991 ◽  
Vol 2 (11) ◽  
pp. 939-949 ◽  
Author(s):  
L J Rizzolo
Keyword(s):  
Retinal Pigment Epithelium ◽  
Basement Membrane ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Collagen Iv ◽  
Membrane Receptors ◽  
Bruch's Membrane ◽  
Bruch’S Membrane ◽  
Developmental Age

The basement membrane stimulates the differentiation and polarity of simple transporting epithelia. We demonstrated for the retinal pigment epithelium (RPE) of chicken embryos that polarity develops gradually. Although the RPE and an immature basement membrane are established on embryonic day 4 (E4), the distribution of the Na,K-ATPase and a family of basement membrane receptors containing the beta 1 subunit of integrin is nonpolarized. The percentage of polarized cells increases gradually until cells in all regions of the epithelium are polarized on E11. During this time, the basement membrane increases in size and complexity to form Bruch's membrane. To study the ability of the basement membrane to stimulate the polarized distribution of the beta 1 integrins or the Na,K-ATPase, RPE was harvested from E7, E9, or E14 embryos and cultured on Bruch's membrane isolated (in association with the choroid) from E14 embryos. As a control, the RPE was plated on the side of the choroid lacking a Bruch's membrane. The distribution of the beta 1 integrins and the Na,K-ATPase was determined by indirect immunofluorescence. Bruch's membrane stimulated the polarized distribution of the beta 1 integrins regardless of the developmental age of the RPE even though E7 RPE is nonpolarized in vivo. To examine the role of individual matrix components, RPE was plated on matrix-coated filters. The polarized distribution of the beta 1 integrins was stimulated by laminin, collagen IV, and Matrigel but not by fibronectin. Interestingly, laminin and collagen IV are present in the basement membrane on E4 when RPE is not polarized in vivo. Under no circumstances was the distribution of the Na,K-ATPase polarized. These data indicate that the basement membrane influences the distribution of a subset of plasma membrane proteins but that other factors are required for full polarity.

scholarly journals Three-Dimensional Characterization of Peripapillary Retinal Pigment Epithelium-Basement Membrane Layer in Patients following Lumbar Puncture

2020 ◽  
Vol 10 (5) ◽  
pp. 1559
Author(s):  
Junfei Tong ◽  
Pengfei Dong ◽  
Sachin Kedar ◽  
Deepta Ghate ◽  
Linxia Gu
Keyword(s):  
Optic Nerve ◽  
Retinal Pigment Epithelium ◽  
Linear Regression ◽  
Basement Membrane ◽  
Optic Nerve Head ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Three Dimensional ◽  
Automatic Method ◽  
Before And After

Purpose: To develop and test an innovative semi-automatic method for quantifying the three-dimensional morphology of the peripapillary retinal pigment epithelium-basement membrane (ppRPE/BM) layer, with application to lumbar puncture (LP) patients. Methods: Nineteen patients undergoing LP were recruited. The optic nerve head images of both eyes were acquired in 12 radial directions using optical coherence tomography (OCT) before and after LP. For each OCT image, the ppRPE/BM layer was automatically segmented with manual corrections by independent graders when necessary. The linear regression model of the ppRPE/BM layer was fitted using the least squares approach, and the ppRPE/BM layer angle was measured as the slope of the linear regression line. The Bland–Altman plots and intraclass correlations (ICC) were used to assess the inter-observer reliabilities in measuring the ppRPE/BM layer angle. The repeated measures ANOVA analysis was applied to determine whether the ppRPE/BM layer angle changes following LP varied across the radial directions. Results: The percentages of scans that required manual corrections were 24% and 32% in the right eyes and left eyes, respectively. The Bland–Altman plots and ICC demonstrated excellent inter-observer reliability. The ppRPE/BM layer angle varied significantly across the 12 radial OCT scanning directions both before and after LP. However, the LP-induced changes in the ppRPE/BM layer angle across different radial directions were not statistically significant (p-value > 0.01). Conclusions: The three-dimensional quantifications of the ppRPE/BM layer angles, enabled by the semi-automatic method, provided enhanced information of the optic nerve head structure. For LP patients, the ppRPE/BM layer angle changes following the LP did not vary significantly across various radial directions, indicating that it could be evaluated in any radial direction.

scholarly journals Grape Seed Proanthocyanindin Extract Moderated Retinal Pigment Epithelium Cellular Senescence Through NAMPT/SIRT1/NLRP3 Pathway

2021 ◽  
Author(s):  
Yan Wu ◽  
Sanyou Dai ◽  
Yang Long ◽  
Hongzhuo Liu ◽  
Weiwei Wan ◽  
...  
Keyword(s):  
Retinal Pigment Epithelium ◽  
Cellular Senescence ◽  
Barrier Function ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Grape Seed ◽  
Rpe Cells ◽  
Mitochondrial Homeostasis

Abstract Background: Cellular senescence of retinal pigment epithelium (RPE) cell was an important cause of degenerative retinal disorders, however, the potential effects of grape seed proanthocyanindin extract (GSPE) through regulating NAMPT/SIRT1/NLRP3 pathway remained unclear.Methods: The effects of GSPE on the cellular senescence biomarkers as well as NAMPT and NAD+ contents were detected in both in-vivo and in-vitro RPE cell models. The protection of GSPE treatment on the mitochondrial homeostasis and barrier function of RPE cells were detected with mtDNA lesions, JC-1 staining, ZO1 expression, trans-epithelial cell resistance (TEER) as well as senescence-associated secretory phenotype (SASP) expressions. The GSPE treatment with NAMPT inhibitor, Fk866, and SIRT1 inhibitor, EX-527, was used in the potential NAMPT/SIRT1/NLRP3 mechanism detection.Results: GSPE significantly improve the NAMPT and NAD+ content in aging mice and thus alleviated the RPE cellular senescence. In advanced in-vitro studies, GSPE could be an activator of NAMPT and thus relieved H2O2 induced NAD+ depression. In advanced analyses, it was reported that GSPE could alleviate mitochondrial homeostasis, barrier function and SASP of aging RPE cells. Thus, detection the SASP in in-vitro aging model provided us knowledge in the understanding of the anti-aging role of GSPE and following detailed pathological mechanism analyses demonstrated that GSPE demonstrated the protective effects in aging RPE cells through NAMPT/SIRT1/NLRP3 pathway.Conclusions: These findings indicate that GSPE alleviated cellular senescence both in-vivo and in-vitro through NAMPT/SIRT1/NLRP3 pathway. This study highlighted the importance both the potential GSPE in degenerative retinopathy as well as the crosstalk of NAD+ metabolism, SIRT1 function and NLRP3 activation.

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