Epithelial–mesenchymal transition of the retinal pigment epithelium causes choriocapillaris atrophy

摘要: Epithelial-to-mesenchymal transition (EMT) of the retinal pigment epithelium (RPE) is commonly observed at sites choroidal neovascularization in patients suffering from age-related macular degeneration. To learn an experimental model how RPE EMT affects biology vasculature, we studied transgenic mice (βB1-TGF-β1) with ocular overexpression transforming growth factor-β1 (TGF-β1). was detectable postnatal day (P)1 and included marked structural functional alterations such as loss outer blood–retina barrier reduced mRNA expression RPE-characteristic molecules Rlbp1, Rpe65, Rbp1 Vegfa. Moreover, vascular endothelial factor (VEGF) not by immunohistochemistry RPE/choroid interface, while cells stained intensely for α-smooth muscle actin. The choriocapillaris, characteristic capillary network adjacent to RPE, developed normally obviously changed embryonic eyes but absent P1 indicating its atrophy. At around same time, photoreceptors stopped differentiate photoreceptor apoptosis abundant second week life. Structural changes were also seen vasculature animals, which did form intraretinal vessels, hyaloid regress. In addition, amounts HIF-1α markedly reduced. We conclude that high active TGF-β1 mouse eye cause transdifferentiation a mesenchymal phenotype. epithelial differentiation leads diminished synthesis including VEGF. Lack RPE-derived VEGF causes atrophy scenario disrupts finally results apoptosis. vessel formation regression might be caused decrease metabolic requirements neuroretina leading low HIF-1α. summary, our data indicate failure may well precede choriocapillaris. contrast, sufficient neovascularization.