Abstract
Purpose: :
Most photosensitizers (PS) used in PDT induce vascular effects during and/or after light exposure of the tissue containing the PS. The main target of vascular PDT appears to be the endothelial cell. Changes to these cells following PDT can result in the release of von Willebrand factor, thromboxane, prostacyclin, and other factors. PDT–induced changes to the cell cytoskeleton may also alter cell shape. Altered endothelial cells may modulate smooth–muscle–cell calcium balance, possibly causing vascular contraction; both rounding and contraction of endothelial cells have been observed (Fingar VH, J Clin Laser Med Surg, 1996). As a result, interendothelial cell tight junctions may loosen, exposing the subendothelial tissue. At the gaps between the rounded endothelial cells, activated platelets adhere, aggregate, and begin to plug the vessel (Andre P, et al. Blood, 2000). Observations of the human choroid demonstrate that PDT closes smaller vessels more easily than larger vessels. The goal of the present study was to visualize and record the vascular thrombosis in real time using PDT with verteporfin (Visudyne®).
Methods: :
The chorioallantoic membrane (CAM) of the chick embryo is a model system in which vessel occlusion, and many other aspects of clinical PDT, is well reproduced (Lange N, et al. IOVS, 2001), using intravenous injection of various PSs and varying drug and light doses. Generally, the larger the light and drug dose of PDT with a PS, the larger the diameter of the vessels that can be occluded. We video–recorded such a thrombosis in real time in our experimental setup using an ultra–high–sensitivity video camera (EM–CCD, Hamamatsu).
Results: :
The video recording permitted monitoring of the location, aggregation, and release of platelets, with an end result of selective vascular closure.
Conclusions: :
An ultra–high–sensitivity video camera allowed us to record such a thrombosis on the CAM model, under conditions close to the clinical setting, with similar drug and light doses of verteporfin therapy. Initial results from an on–going study on the normal vasculature of nude mice, using the dorsal skin fold chamber model, will also be presented.
Keywords: photodynamic therapy • vascular occlusion/vascular occlusive disease • choroid: neovascularization