Serous business: Delineating the broad spectrum of diseases with subretinal fluid in the macula

Dijk, Elon H. C. van; Boon, Camiel J F

doi:10.1016/j.preteyeres.2021.100955

Cited by 46 publications

(63 citation statements)

References 478 publications

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“…The localization of the SRF often correlates with hyperfluorescent changes on ICGA, which are presumed to reflect vascular hyperpermeability of the choriocapillaris (Prünte 1995 ; Teussink et al. 2015 ; van Dijk & Boon 2021 ; van Rijssen et al. 2021a ).…”

Section: The Pachychoroid Disease Spectrum: Venous Overload Of Myster...mentioning

confidence: 99%

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Choroidal arteriovenous anastomoses: a hypothesis for the pathogenesis of central serous chorioretinopathy and other pachychoroid disease spectrum abnormalities

Brinks

Dijk

Meijer

et al. 2022

Acta Ophthalmologica

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The pachychoroid disease spectrum (PDS) includes several chorioretinal diseases that share specific choroidal abnormalities. Although their pathophysiological basis is poorly understood, diseases that are part of the PDS have been hypothesized to be the result of venous congestion. Within the PDS, central serous chorioretinopathy is the most common condition associated with vision loss, due to an accumulation of subretinal fluid in the macula. Central serous chorioretinopathy is characterized by distinct risk factors, most notably a high prevalence in males and exposure to corticosteroids. Interestingly, sex differences and corticosteroids are also strongly associated with specific types of arteriovenous anastomoses in the human body, including dural arteriovenous fistula and surgically created arteriovenous shunts. In this manuscript, we assess the potential of such arteriovenous anastomoses in the choroid as a causal mechanism of the PDS. We propose how this may provide a novel unifying concept on the pathophysiological basis of the PDS, and present cases in which this mechanism may play a role.

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Section: The Pachychoroid Disease Spectrum: Venous Overload Of Myster...mentioning

confidence: 99%

“… 2019 ; Mohabati et al. 2020a ; van Dijk & Boon 2021 ). Chronic CSC commonly shows multifocal leakage and more widespread RPE abnormalities on FA compared with acute CSC, as well as more extensive multifocal choroidal abnormalities on ICGA (van Rijssen et al.…”

Section: Arteriovenous Anastomoses and Fistula In The Pachychoroid Di...mentioning

confidence: 99%

Choroidal arteriovenous anastomoses: a hypothesis for the pathogenesis of central serous chorioretinopathy and other pachychoroid disease spectrum abnormalities

Brinks

Dijk

Meijer

et al. 2022

Acta Ophthalmologica

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“…These choroidal changes are presumed to damage the outer blood-retinal barrier, which is formed by the tight junctions of the RPE, leading to the fluid accumulation under the retina ( 8 , 9 ). This fluid often preferentially occurs in the cone photoreceptor-rich central area of the retina due to its specific anatomical and functional characteristics ( 10 ). As such, this subretinal fluid can lead to irreversible damage to photoreceptors, visual loss, and loss of quality of life ( 11 ).…”

mentioning

confidence: 99%

The Cortisol Response of Male and Female Choroidal Endothelial Cells: Implications for Central Serous Chorioretinopathy

Brinks

Dijk

Kiełbasa

et al. 2021

The Journal of Clinical Endocrinology &Amp; Metabolism

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Context Central serous chorioretinopathy (CSC) is a severe ocular disease characterized by fluid accumulation under the retina and abnormalities in the underlying vascular layer, the choroid. CSC has a striking prevalence in males of 80-90% of total patients. Corticosteroids are the most pronounced extrinsic risk factor for CSC. Choroidal endothelial cells (CECs) are important for the vascular integrity of the choroid, but the effects of corticosteroid effects in these cells are unknown. Design and Objective We aimed to reveal the potential steroidal contribution to CSC. We characterized the expression of the glucocorticoid-, mineralocorticoid-, and androgen receptor in the human choroid, using immunohistochemistry. Using RNA-sequencing, we describe the cortisol response in human CECs derived from 5 male and 5 female postmortem donors. Results The glucocorticoid receptor was highly expressed in the human choroid, whereas no to minimal expression of the mineralocorticoid- and androgen receptors was observed. The extensive transcriptional response to cortisol in human primary cultured CECs showed interindividual differences, but very few sex differences. Several highly regulated genes such as ZBTB16 (log2 fold change males 7.9; females 6.2) provide strong links to choroidal vascular regulation. Conclusions The glucocorticoid receptor predominantly mediates the response to cortisol in human CECs. Interindividual differences are an important determinant regarding the cortisol response in human cultured CECs, whereas intrinsic sex differences appear less pronounced. The marked response of particular target genes in endothelial cells to cortisol, such as ZBTB16, warrants further investigation into their potential role in the pathophysiology of CSC and other vascular conditions.

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“…Hyporeflective regions were apparent even at 1 and 2 months of age (Figures 3G,H and 4D,E, arrowheads; Videos S2-S4). In OCT scans of human patients and animal models, hyporeflective areas between the retina and RPE indicate subretinal fluid, associated with pathological [53,54], post-surgical [55], or experimentally induced retinal detachment [56].…”

Section: Retinal Detachment and Layer Thinningmentioning

confidence: 99%

A Splicing Mutation in Slc4a5 Results in Retinal Detachment and Retinal Pigment Epithelium Dysfunction

Collin

Shi

et al. 2022

IJMS

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Fluid and solute transporters of the retinal pigment epithelium (RPE) are core components of the outer blood–retinal barrier. Characterizing these transporters and their role in retinal homeostasis may provide insights into ocular function and disease. Here, we describe RPE defects in tvrm77 mice, which exhibit hypopigmented patches in the central retina. Mapping and nucleotide sequencing of tvrm77 mice revealed a disrupted 5’ splice donor sequence in Slc4a5, a sodium bicarbonate cotransporter gene. Slc4a5 expression was reduced 19.7-fold in tvrm77 RPE relative to controls, and alternative splice variants were detected. SLC4A5 was localized to the Golgi apparatus of cultured human RPE cells and in apical and basal membranes. Fundus imaging, optical coherence tomography, microscopy, and electroretinography (ERG) of tvrm77 mice revealed retinal detachment, hypopigmented patches corresponding to neovascular lesions, and retinal folds. Detachment worsened and outer nuclear layer thickness decreased with age. ERG a- and b-wave response amplitudes were initially normal but declined in older mice. The direct current ERG fast oscillation and light peak were reduced in amplitude at all ages, whereas other RPE-associated responses were unaffected. These results link a new Slc4a5 mutation to subretinal fluid accumulation and altered light-evoked RPE electrophysiological responses, suggesting that SLC4A5 functions at the outer blood–retinal barrier.

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Serous business: Delineating the broad spectrum of diseases with subretinal fluid in the macula

Cited by 46 publications

References 478 publications

Choroidal arteriovenous anastomoses: a hypothesis for the pathogenesis of central serous chorioretinopathy and other pachychoroid disease spectrum abnormalities

Choroidal arteriovenous anastomoses: a hypothesis for the pathogenesis of central serous chorioretinopathy and other pachychoroid disease spectrum abnormalities

The Cortisol Response of Male and Female Choroidal Endothelial Cells: Implications for Central Serous Chorioretinopathy

A Splicing Mutation in Slc4a5 Results in Retinal Detachment and Retinal Pigment Epithelium Dysfunction

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