Cadherin 5 is regulated by corticosteroids and associated with central serous chorioretinopathy.
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.
Affiliation: Department of Ophthalmology, Columbia University, New York City, New York.Show MeSH
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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.
Affiliation: Department of Ophthalmology, Columbia University, New York City, New York.