latrunculin-a and Glaucoma

Primary open-angle glaucoma is associated with elevated intraocular pressure (IOP) that damages the optic nerve and leads to gradual vision loss. Several agents that reduce the stiffness of pressure-regulating Schlemm's canal (SC) endothelial cells, in the conventional outflow pathway of the eye, lower IOP in glaucoma patients and are approved for clinical use. However, poor drug penetration and uncontrolled biodistribution limit their efficacy and produce local adverse effects. Compared to other ocular endothelia, FLT4/VEGFR3 is expressed at elevated levels by SC endothelial cells and can be exploited for targeted drug delivery. Here, we validate FLT4 receptors as clinically relevant targets on SC cells from glaucomatous human donors and engineer polymeric self-assembled nanocarriers displaying lipid-anchored targeting ligands that optimally engage this receptor. Targeting constructs were synthesized as lipid-PEG

Topics: Actins; Aged; Animals; Bridged Bicyclo Compounds, Heterocyclic; Drug Carriers; Endothelial Cells; Female; Glaucoma; Human Umbilical Vein Endothelial Cells; Humans; Intraocular Pressure; Limbus Corneae; Male; Mice, Inbred C57BL; Micelles; Molecular Structure; Peptides; Polyethylene Glycols; Sulfides; Thiazolidines; Vascular Endothelial Growth Factor Receptor-3