Glucocorticoids exert differential effects on the endothelium in an <i>in vitro</i> model of the blood–retinal barrier

Wijk, A. van; Canning, Paul; Heijningen, Rutger P. van; Vogels, I. M. C.; Noorden, C. J. F. Van; Klaassen, Ingeborg; Schlingemann, Reinier O.

doi:10.1111/aos.13909

Cited by 10 publications

(4 citation statements)

References 52 publications

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“…A positive correlation was registered between differential light sensitivity and the cumulative dose of corticosteroids in our study population, supporting a potential protective role of steroids in maintaining retinal function in course of a systemic inflammatory disease [41]. However, it should be noted that perimetric indices of visual field can be affected by the significant ocular discomfort of PsA patients, in accordance with the literature reporting that the better tear film stability the higher optical quality of the anterior corneal surface [41]. Published studies showed that dry corneal surfaces can certainly affect the SAP findings [42][43][44].…”

Section: Discussionsupporting

confidence: 77%

“…Since no correlation between age and the retinal sensitivity was observed in controls, it is likely that, in PsA patients, the abnormal retinal sensitivity function can be related to a potential damage in retinal structures detectable in chronic diseases [37,40]. A positive correlation was registered between differential light sensitivity and the cumulative dose of corticosteroids in our study population, supporting a potential protective role of steroids in maintaining retinal function in course of a systemic inflammatory disease [41]. However, it should be noted that perimetric indices of visual field can be affected by the significant ocular discomfort of PsA patients, in accordance with the literature reporting that the better tear film stability the higher optical quality of the anterior corneal surface [41].…”

Section: Discussionmentioning

confidence: 49%

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A Multimodal Eye Assessment in Psoriatic Arthritis Patients sine-Psoriasis: Evidence for a Potential Association with Systemic Inflammation

Chimenti

Triggianese

Salandri

et al. 2020

JCM

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Background: Ocular involvement in Psoriatic Arthritis (PsA) patients is mainly associated with uveitis but there remains a paucity of data on dry eye and retinal abnormalities. We aimed to analyze dry eye and subclinical retinal abnormalities in a cohort of PsA patients sine-psoriasis (PsO). Methods: PsA patients sine-PsO were enrolled. Best-corrected-visual-acuity, ocular-surface-disease-index (OSDI), Schirmer test, tear film breakup-time, standard-automated-perimetry (SAP, mean deviation—MD, pattern standard deviation—PSD), fundus-perimetry (FP), and spectral-domain-optical-coherence-tomography (SD-OCT) were performed. Results: A total of 80 eyes from 40 PsA patients with moderate-severe disease activity, and 70 eyes from 35 healthy control (HC) were evaluated. Higher dry eye prevalence occurred in PsA than HC (p < 0.0001). ESR was positively related with OSDI (p < 0.001) and negatively related with Schirmer (p = 0.007). In PsA, SAP registered higher MD (p < 0.0001) and higher PSD (p = 0.005) in comparison with HC. PSD resulted positively correlated with ESR (p = 0.04) and CRP (p = 0.01), while MD showed a negative correlation with CRP (p = 0.01). Both FP mean differential sensitivity and mean defect were lower in PsA then HC (p < 0.0001). In PsA, FP differential sensitivity was directly related with cumulative steroids (p = 0.02). Conclusions: In PsA patients sine-PsO, dry eye and subclinical abnormalities in visual functions occurred being potentially related to systemic inflammation.

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Section: Discussionsupporting

confidence: 77%

Section: Discussionmentioning

confidence: 49%

A Multimodal Eye Assessment in Psoriatic Arthritis Patients sine-Psoriasis: Evidence for a Potential Association with Systemic Inflammation

Chimenti

Triggianese

Salandri

et al. 2020

JCM

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“…In the present study, ALD and HC significantly increased the gene expression of ZO-1 , coding a well-known tight junction-associated protein and adherens junction protein, which could affect the Na-F transport. A previous report demonstrated increased expression of ZO-1, occludin, and claudin-5 by glucocorticoids in primary bovine retinal endothelial cells 29 . Although immunohistochemistry did not reflect the increased gene expression of ZO-1 in this study, the integrity of the tight junction is an important factor in paracellular transport.…”

Section: Discussionmentioning

confidence: 80%

Increased sodium fluorescein transport by corticosteroids is inhibited by a LAT-1 specific inhibitor in retinal pigment epithelial cells in vitro

Misawa,

Honda

2023

Sci Rep

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To investigate whether aldosterone (ALD) and hydrocortisone (HC) change the gene expression of SLC7A5, which encodes the large neutral amino acid transporter small subunit 1 (LAT1), and the transport activity of LAT1 in the retinal pigment epithelium (RPE) in vitro. ARPE-19 cells were grown to confluence. After withdrawing the serum, ALD or HC was added with several doses and incubated, and SLC7A5 gene expression was measured. The influx and efflux transport of sodium fluorescein (Na-F) were evaluated using the Transwell culture system. SLC7A5 gene expression was upregulated by ALD and downregulated by HC in a dose-dependent manner. Both ALD and HC significantly increased the influx and efflux Na-F transport of RPE cells at a dose that did not change the expression of SLC7A5. JPH203, a specific inhibitor of LAT1, significantly reduced accelerated Na-F transport. Both ALD and HC increased the gene expression of zonula occludin-1 (ZO-1) although they did not change the immunoreactivity of ZO-1 in RPE cells. LAT1 may play an important role in increasing Na-F transport associated with ALD and HC administration. A specific LAT1 inhibitor may effectively regulate the increased material transport of RPE induced by ALD and HC.

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“…In general, out of 128 OEMR patients, on whom information on radiation was available, only a minority of 17 patients (13%) received local irradiation (n = 15) or local radiation combined with TBI (n = 2) whereas the majority did not (Supplementary Table S2). As an exception, relapses within the eye have been considered as specific local risk being potentially protected from chemotherapeutic agents by a blood-retina barrier [35]. Three out of four patients with ocular relapses received irradiation of the eye.…”

Section: Oemr Shows a Distinct Event Pattern Compared To Non-oemrmentioning

confidence: 99%

Other (Non-CNS/Testicular) Extramedullary Localizations of Childhood Relapsed Acute Lymphoblastic Leukemia and Lymphoblastic Lymphoma—A Report from the ALL-REZ Study Group

Lissat

Schewick

Steffen

et al. 2021

JCM

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Children with other extramedullary relapse of acute lymphoblastic leukemia are currently poorly characterized. We aim to assess the prevalence and the clinical, therapeutic and prognostic features of extramedullary localizations other than central nervous system or testis in children with relapse of acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma (LBL) treated on a relapsed ALL protocol. Patients and Methods: Patients with relapse of ALL and LBL, treated according to the multicentric ALL-REZ BFM trials between 1983 and 2015, were analyzed for other extramedullary relapse (OEMR) of the disease regarding clinical features, treatment and outcome. Local treatment/irradiation has been recommended on an individual basis and performed only in a minority of patients. Results: A total of 132 out of 2323 (5.6%) patients with ALL relapse presented with an OEMR (combined bone marrow relapse n = 78; isolated extramedullary relapse n = 54). Compared to the non-OEMR group, patients with OEMR had a higher rate of T-immunophenotype (p < 0.001), a higher rate of LBL (p < 0.001) and a significantly different distribution of time to relapse, i.e., more very early and late relapses compared to the non-OEMR group (p = 0.01). Ten-year probabilities of event-free survival (pEFS) and overall survival (pOS) in non-OEMR vs. OEMR were 0.38 ± 0.01 and 0.32 ± 0.04 (p = 0.0204) vs. 0.45 ± 0.01 and 0.37 ± 0.04 (p = 0.0112), respectively. OEMRs have been classified into five subgroups according to the main affected compartment: lymphatic organs (n = 32, 10y-pEFS 0.50 ± 0.09), mediastinum (n = 35, 10y-pEFS 0.11 ± 0.05), bone (n = 12, 0.17 ± 0.11), skin and glands (n = 21, 0.32 ± 0.11) and other localizations (n = 32, 0.41 ± 0.09). Patients with OEMR and T-lineage ALL/LBL showed a significantly worse 10y-pEFS (0.15 ± 0.04) than those with B-Precursor-ALL (0.49 ± 0.06, p < 0.001). Stratified into standard risk (SR) and high risk (HR) groups, pEFS and pOS of OEMR subgroups were in the expected range whereas the mediastinal subgroup had a significantly worse outcome. Subsequent relapses involved more frequently the bone marrow (58.4%) than isolated extramedullary compartments (41.7%). In multivariate Cox regression, OEMR confers an independent prognostic factor for inferior pEFS and pOS. Conclusion: OEMR is adversely related to prognosis. However, the established risk classification can be applied for all subgroups except mediastinal relapses requiring treatment intensification. Generally, isolated OEMR of T-cell-origin needs an intensified treatment including allogeneic stem cell transplantation (HSCT) as a curative approach independent from time to relapse. Local therapy such as surgery and irradiation may be of benefit in selected cases. The indication needs to be clarified in further investigations.

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Glucocorticoids exert differential effects on the endothelium in an in vitro model of the blood–retinal barrier

Abstract: Glucocorticoids have differential effects in an experimental in vitro BRB model. TA is the most potent in improving barrier function, both at the molecular and functional levels, and TA prevents VEGF-induced expression of PLVAP.

Cited by 10 publications

References 52 publications

A Multimodal Eye Assessment in Psoriatic Arthritis Patients sine-Psoriasis: Evidence for a Potential Association with Systemic Inflammation

A Multimodal Eye Assessment in Psoriatic Arthritis Patients sine-Psoriasis: Evidence for a Potential Association with Systemic Inflammation

Increased sodium fluorescein transport by corticosteroids is inhibited by a LAT-1 specific inhibitor in retinal pigment epithelial cells in vitro

Other (Non-CNS/Testicular) Extramedullary Localizations of Childhood Relapsed Acute Lymphoblastic Leukemia and Lymphoblastic Lymphoma—A Report from the ALL-REZ Study Group

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