| First Author | Strittmatter K | Year | 2016 |
| Journal | Am J Pathol | Volume | 186 |
| Issue | 7 | Pages | 1890-9 |
| PubMed ID | 27338108 | Mgi Jnum | J:234267 |
| Mgi Id | MGI:5789657 | Doi | 10.1016/j.ajpath.2016.02.018 |
| Citation | Strittmatter K, et al. (2016) Targeting Platelet-Derived Growth Factor Receptor beta(+) Scaffold Formation Inhibits Choroidal Neovascularization. Am J Pathol 186(7):1890-9 |
| abstractText | Neovascular age-related macular degeneration is among the most common causes of irreversible blindness and manifests with choroidal neovascularization (CNV). Anti-vascular endothelial growth factor-A therapies are only partially effective and their chronic administration may impair functions of the choriocapillaris and retina. Thus, novel therapeutic targets are needed urgently. We have observed in a laser-induced model of CNV that a platelet-derived growth factor receptor beta positive (PDGFRbeta(+)) scaffold is formed before infiltration of neovessels into this scaffold to form CNV lesions, and that this scaffold limits the extent of neovascularization. Based on these observations we hypothesized that ablation of proliferating PDGFRbeta(+) cells to prevent the formation of this scaffold might inhibit CNV growth and present a novel therapeutic approach for neovascular age-related macular degeneration. To test this hypothesis we targeted proliferating PDGFRbeta(+) cells through independent distinct approaches after laser injury: i) by using an inducible genetic model to inhibit specifically proliferating PDGFRbeta(+) cells, ii) by treating mice with a neutralizing anti-PDGFRbeta antibody, iii) by administering an anti-PDGF-AB/BB aptamer, and iv) by using small chemical inhibitor approaches. The results show that therapeutic targeting of proliferating PDGFRbeta(+) cells potently inhibits the formation of the pericyte-like scaffold, with concomitant attenuation of CNV. Moreover, we show that early inhibition of PDGFRbeta(+) cell proliferation before neovessel formation is sufficient to inhibit scaffold formation and neovascularization. |
