| First Author | Wang H | Year | 2016 |
| Journal | Invest Ophthalmol Vis Sci | Volume | 57 |
| Issue | 13 | Pages | 5525-5534 |
| PubMed ID | 27768790 | Mgi Jnum | J:254683 |
| Mgi Id | MGI:6112514 | Doi | 10.1167/iovs.16-19691 |
| Citation | Wang H, et al. (2016) Thy-1 Regulates VEGF-Mediated Choroidal Endothelial Cell Activation and Migration: Implications in Neovascular Age-Related Macular Degeneration. Invest Ophthalmol Vis Sci 57(13):5525-5534 |
| abstractText | Purpose: This study addresses the hypothesis that age-related stresses upregulate Thy-1 in choroidal endothelial cells (CECs) and contribute to CEC activation and migration, processes important in choroidal neovascularization (CNV). Methods: Measurements were made of Thy-1 protein (Western blot) in CECs and Thy-1 mRNA (real time quantitative PCR) in CECs treated with VEGF, CCL11, or PBS or in RPE/choroids from young or old donors or lasered or nonlasered mice. Immunolabeled Thy-1 in ocular sections was compared from young versus old human donor eyes or those with or without neovascular AMD or from lasered versus nonlasered mice. Choroidal endothelial cells transfected with Thy-1 or control siRNA or pretreated with Thy-1 blocking peptide or control were stimulated with VEGF or 7-ketocholesterol (7-KC). Choroidal endothelial cell migration, proliferation, cytoskeletal stress fibers, Rac1 activation, and phosphorylated VEGF receptor 2 (VEGFR2), integrin beta3, and Src were measured. Statistics were performed using ANOVA. Results: Thy-1 was expressed in retinal ganglion cells and in vascular endothelial-cadherin-labeled choroid and localized to human or mouse laser-induced CNV lesions. Thy-1 protein and mRNA were significantly increased in CECs treated with VEGF or CCL11 and in RPE/choroids from aged versus young donor eyes or from lasered mice versus nonlasered controls. Knockdown or inhibition of Thy-1 in CECs significantly reduced VEGF-induced CEC migration and proliferation, stress fiber formation and VEGFR2, Src, integrin beta3 and Rac1 activation, and 7-KC-induced Rac1 and Src activation. Conclusions: Thy-1 in CECs regulates VEGF-induced CEC activation and migration and links extracellular 7-KC to intracellular signaling. Future studies elucidating Thy-1 mechanisms in neovascular AMD are warranted. |
