title: Complete blood vessel occlusion in the chick chorioallantoic membrane using two-photon excitation photodynamic therapy: implications for treatment of wet age-related macular degeneration.
abstract: Complete blood vessel occlusion is required for the treatment of age-related macular degeneration (AMD). AMD is the leading cause of blindness in developed countries and current treatment regimes have potential to cause collateral damage, or do not remove pre-existing unwanted vasculature. It has been proposed that two-photon excitation (TPE) photodynamic therapy (PDT) can be applied to cause local blood vessel occlusion without damaging surrounding retinal tissues. The in ovo chicken chorioallantoic membrane (CAM) is used as the model for vascularization in the wet form of AMD; novel techniques for the utilization of the CAM are reported. Complete occlusion of CAM vessels approximately 15 microm in diameter is achieved using the clinically approved photosensitizer Verteporfin (Visudyne, QLT, Incorporated, Vancouver, British Columbia, Canada) and TPE activation. The average and peak irradiances used for treatment are 3.3x10(6) Wcm(2) and 3.7x10(11) Wcm(2), respectively. A total fluence of 1.1x10(8) Jcm(2) is the dosage required for successful occlusion, and it is expected that for optimal conditions it will be much less. These results are the first proof-of-principle evidence in the literature that indicate TPE-PDT can be used to occlude small blood vessels. Further investigation will help determine the utility of TPE-PDT for treating wet AMD, perhaps through targeting feeder vessels.
authors.affiliation: University of Calgary, Department of Chemistry, 2500 University Drive, Northwest, Calgary, Alberta T2N 1N4, Canada.
authors.forename: Kimberley S
authors.initials: KS
authors.lastname: Samkoe
authors.forename: Aisling A
authors.initials: AA
authors.lastname: Clancy
authors.forename: Aliaksandr
authors.initials: A
authors.lastname: Karotki
authors.forename: Brian C
authors.initials: BC
authors.lastname: Wilson
authors.forename: David T
authors.initials: DT
authors.lastname: Cramb
mesh_terms: D000818:Animals; D001808:Blood Vessels / Q000187:drug effects* / Q000528:radiation effects; D002642:Chick Embryo; D049033:Chorioallantoic Membrane / Q000098:blood supply* / Q000187:drug effects* / Q000473:pathology / Q000528:radiation effects; D006801:Humans; D066298:In Vitro Techniques; D008268:Macular Degeneration / Q000188:drug therapy* / Q000473:pathology; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000008:administration & dosage; D011166:Porphyrins / Q000008:administration & dosage*; D000077362:Verteporfin
chemical_list: D017319:Photosensitizing Agents; D011166:Porphyrins; D000077362:Verteporfin