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Cadherin 5 is regulated by corticosteroids and associated with central serous chorioretinopathy.

Schubert C, Pryds A, Zeng S, Xie Y, Freund KB, Spaide RF, Merriam JC, Barbazetto I, Slakter JS, Chang S, Munch IC, Drack AV, Hernandez J, Yzer S, Merriam JE, Linneberg A, Larsen M, Yannuzzi LA, Mullins RF, Allikmets R - Hum. Mutat. (2014)

Bottom Line: We found a significant association of four common CDH5 SNPs with CSC in male patients in both cohorts.Two common intronic variants, rs7499886:A>G and rs1073584:C>T, exhibit strongly significant associations with CSC; P = 0.00012; odds ratio (OR) = 1.5; 95%CI [1.2;1.8], and P = 0.0014; OR = 0.70; 95%CI [0.57;0.87], respectively.We propose that genetically predetermined variation in CDH5, when combined with triggering events such as corticosteroid treatment or severe hormonal imbalance, underlie a substantial proportion of CSC in the male population.

View Article: PubMed Central - PubMed

Affiliation: Department of Ophthalmology, Columbia University, New York City, New York.

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Related in: MedlinePlus

Anatomy of intercellular endothelial junctions in organ cultures of human RPE-choroid. A–C: Choriocapillaris endothelial cell junctions. In each case the vascular lumen (asterisk) is oriented toward the bottom of the micrograph. Compared with the control cultures (A), cultures treated with prednisolone displayed more EC junctions with misaligned or overhanging adjacent leaflets (B, arrow). In rare cases, there was a gap between the EC leaflets in steroid treated cultures (C, arrow). Scale bar = 500 nm. D: Distribution of junctions in control and prednisolone treated cultures in the outer choroid. Prednisolone treated cultures exhibited decreased junction size (P < 0.05).
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fig04: Anatomy of intercellular endothelial junctions in organ cultures of human RPE-choroid. A–C: Choriocapillaris endothelial cell junctions. In each case the vascular lumen (asterisk) is oriented toward the bottom of the micrograph. Compared with the control cultures (A), cultures treated with prednisolone displayed more EC junctions with misaligned or overhanging adjacent leaflets (B, arrow). In rare cases, there was a gap between the EC leaflets in steroid treated cultures (C, arrow). Scale bar = 500 nm. D: Distribution of junctions in control and prednisolone treated cultures in the outer choroid. Prednisolone treated cultures exhibited decreased junction size (P < 0.05).

Mentions: When human RPE-choroid organ cultures were exposed to prednisolone, the expression levels of CDH5 were significantly reduced (P = 0.011, fold change >-4×) compared with the control cultures (Fig.3B). In order to assess whether corticosteroid treatment is capable of altering the microanatomy of endothelial cell junctional contacts, transmission electron microscopy was performed on 12 organ cultures (n = 6 prednisolone and n = 6 control) from two donors with no known history of ophthalmic disease. Qualitatively, no obvious changes were noted in RPE cell junctional complexes. The majority of choroidal intercellular junctions appeared grossly similar in steroid-treated and control cultures. However, qualitative alterations in junctional structure were observed in some junctions of the choriocapillaris in prednisolone treated cultures more notably than in control cultures. This included increased overhang of one of the leaflets and/or reduced contact between EC (Fig.4B). In some cases, prednisolone treated cultures showed a substantial gap in the junctional contacts of up to 50 nm (Fig.4C); although relatively rare in steroid-treated cultures, this phenomenon was not observed at all in any of the control cultures.


Cadherin 5 is regulated by corticosteroids and associated with central serous chorioretinopathy.

Schubert C, Pryds A, Zeng S, Xie Y, Freund KB, Spaide RF, Merriam JC, Barbazetto I, Slakter JS, Chang S, Munch IC, Drack AV, Hernandez J, Yzer S, Merriam JE, Linneberg A, Larsen M, Yannuzzi LA, Mullins RF, Allikmets R - Hum. Mutat. (2014)

Anatomy of intercellular endothelial junctions in organ cultures of human RPE-choroid. A–C: Choriocapillaris endothelial cell junctions. In each case the vascular lumen (asterisk) is oriented toward the bottom of the micrograph. Compared with the control cultures (A), cultures treated with prednisolone displayed more EC junctions with misaligned or overhanging adjacent leaflets (B, arrow). In rare cases, there was a gap between the EC leaflets in steroid treated cultures (C, arrow). Scale bar = 500 nm. D: Distribution of junctions in control and prednisolone treated cultures in the outer choroid. Prednisolone treated cultures exhibited decreased junction size (P < 0.05).
© Copyright Policy - open-access
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4215937&req=5

fig04: Anatomy of intercellular endothelial junctions in organ cultures of human RPE-choroid. A–C: Choriocapillaris endothelial cell junctions. In each case the vascular lumen (asterisk) is oriented toward the bottom of the micrograph. Compared with the control cultures (A), cultures treated with prednisolone displayed more EC junctions with misaligned or overhanging adjacent leaflets (B, arrow). In rare cases, there was a gap between the EC leaflets in steroid treated cultures (C, arrow). Scale bar = 500 nm. D: Distribution of junctions in control and prednisolone treated cultures in the outer choroid. Prednisolone treated cultures exhibited decreased junction size (P < 0.05).
Mentions: When human RPE-choroid organ cultures were exposed to prednisolone, the expression levels of CDH5 were significantly reduced (P = 0.011, fold change >-4×) compared with the control cultures (Fig.3B). In order to assess whether corticosteroid treatment is capable of altering the microanatomy of endothelial cell junctional contacts, transmission electron microscopy was performed on 12 organ cultures (n = 6 prednisolone and n = 6 control) from two donors with no known history of ophthalmic disease. Qualitatively, no obvious changes were noted in RPE cell junctional complexes. The majority of choroidal intercellular junctions appeared grossly similar in steroid-treated and control cultures. However, qualitative alterations in junctional structure were observed in some junctions of the choriocapillaris in prednisolone treated cultures more notably than in control cultures. This included increased overhang of one of the leaflets and/or reduced contact between EC (Fig.4B). In some cases, prednisolone treated cultures showed a substantial gap in the junctional contacts of up to 50 nm (Fig.4C); although relatively rare in steroid-treated cultures, this phenomenon was not observed at all in any of the control cultures.

Bottom Line: We found a significant association of four common CDH5 SNPs with CSC in male patients in both cohorts.Two common intronic variants, rs7499886:A>G and rs1073584:C>T, exhibit strongly significant associations with CSC; P = 0.00012; odds ratio (OR) = 1.5; 95%CI [1.2;1.8], and P = 0.0014; OR = 0.70; 95%CI [0.57;0.87], respectively.We propose that genetically predetermined variation in CDH5, when combined with triggering events such as corticosteroid treatment or severe hormonal imbalance, underlie a substantial proportion of CSC in the male population.

View Article: PubMed Central - PubMed

Affiliation: Department of Ophthalmology, Columbia University, New York City, New York.

Show MeSH
Related in: MedlinePlus