Antagonism of PDGF-BB suppresses subretinal neovascularization and enhances the effects of blocking VEGF-A.

Hypoxia-inducible factor-1 (HIF-1) plays an important role in retinal and subretinal neovascularization (NV). Increased levels of HIF-1 cause increased expression of vascular endothelial growth factor (VEGF-A) and current therapies for ocular NV focus on neutralizing VEGF-A, but there is mounting evidence that other HIF-1-responsive gene products may also participate. In this study, we tested the effect of a designed ankyrin repeat protein (DARPin) that selectively binds and antagonizes the hypoxia-regulated gene product PDGF-BB in three models of subretinal NV (relevant to neovascular age-related macular degeneration) and compared its effects to a DARPin that selectively antagonizes VEGF-A.

In vivo targeting of tumor-associated carbonic anhydrases using acetazolamide derivatives.

We describe the synthesis and characterization of two acetazolamide derivatives containing either a charged fluorophore or an albumin-binding moiety, which restrict binding to carbonic anhydrase IX and XII present on tumor cells. In vivo studies showed the preferentially targeting of tumor cells by the fluorescent acetazolamide derivative and the ability of the albumin-binding acetazolamide derivative to cause tumor retardation in a SK-RC-52 xenograft model of cancer.