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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

Immunohistochemical labeling of CDH5 (green fluorescence) in the choroid of an 86-year-old female donor. Note labeling in the choriocapillaris (CC) and at the margins of endothelial cells in larger choroidal vessels. Arrowheads indicate intercellular junctions and asterisks indicate vessel lumens. The yellow autofluorescence in the RPE is due to lipofuscin and the blue fluorescence is due to nuclear counterstaining with DAPI. Scale bar = 50 μm.
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fig02: Immunohistochemical labeling of CDH5 (green fluorescence) in the choroid of an 86-year-old female donor. Note labeling in the choriocapillaris (CC) and at the margins of endothelial cells in larger choroidal vessels. Arrowheads indicate intercellular junctions and asterisks indicate vessel lumens. The yellow autofluorescence in the RPE is due to lipofuscin and the blue fluorescence is due to nuclear counterstaining with DAPI. Scale bar = 50 μm.

Mentions: The protein encoded by the CDH5 gene is a calcium-binding cell–cell adhesion glycoprotein composed of five extracellular cadherin repeats, a transmembrane region and a highly conserved cytoplasmic tail. CDH5 is localized to endothelial cell junctions, including those between endothelial cells in the human choroid. As described for other vascular beds, CDH5 protein was localized to choriocapillaris and larger vessels in Sattler's and Haller's layers of the human choroid. Labeling was notable in larger vessels at the interfaces between individual endothelial cells (Fig.2). Therefore, CDH5 is localized to intercellular junctions also in human eyes where it functions as a classic cadherin allowing choroidal endothelial cells to adhere in a homophilic manner. The protein plays an important role in endothelial cell biology through control of the cohesion and organization of the intercellular junctions. Phosphorylation or decreased mRNA expression are associated with disassembly of CDH5 molecules and increased vascular permeability Dejana et al., 2008; Harris and Nelson, 2010. We investigated the possibility that CDH5 is a plausible candidate gene for CSC by determining whether its expression is affected by corticosteroids in cultured endothelial cells, in human RPE-choroid organ cultures, and in murine eyes in vivo.


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)

Immunohistochemical labeling of CDH5 (green fluorescence) in the choroid of an 86-year-old female donor. Note labeling in the choriocapillaris (CC) and at the margins of endothelial cells in larger choroidal vessels. Arrowheads indicate intercellular junctions and asterisks indicate vessel lumens. The yellow autofluorescence in the RPE is due to lipofuscin and the blue fluorescence is due to nuclear counterstaining with DAPI. Scale bar = 50 μm.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig02: Immunohistochemical labeling of CDH5 (green fluorescence) in the choroid of an 86-year-old female donor. Note labeling in the choriocapillaris (CC) and at the margins of endothelial cells in larger choroidal vessels. Arrowheads indicate intercellular junctions and asterisks indicate vessel lumens. The yellow autofluorescence in the RPE is due to lipofuscin and the blue fluorescence is due to nuclear counterstaining with DAPI. Scale bar = 50 μm.
Mentions: The protein encoded by the CDH5 gene is a calcium-binding cell–cell adhesion glycoprotein composed of five extracellular cadherin repeats, a transmembrane region and a highly conserved cytoplasmic tail. CDH5 is localized to endothelial cell junctions, including those between endothelial cells in the human choroid. As described for other vascular beds, CDH5 protein was localized to choriocapillaris and larger vessels in Sattler's and Haller's layers of the human choroid. Labeling was notable in larger vessels at the interfaces between individual endothelial cells (Fig.2). Therefore, CDH5 is localized to intercellular junctions also in human eyes where it functions as a classic cadherin allowing choroidal endothelial cells to adhere in a homophilic manner. The protein plays an important role in endothelial cell biology through control of the cohesion and organization of the intercellular junctions. Phosphorylation or decreased mRNA expression are associated with disassembly of CDH5 molecules and increased vascular permeability Dejana et al., 2008; Harris and Nelson, 2010. We investigated the possibility that CDH5 is a plausible candidate gene for CSC by determining whether its expression is affected by corticosteroids in cultured endothelial cells, in human RPE-choroid organ cultures, and in murine eyes in vivo.

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