Photodynamic effect of a new photosensitizer ATX-S10 on corneal neovascularization.
In order to elucidate the mechanism by which a new photosensitizer ATX-S10 causes the photodynamic effect on neovasculature, we investigated the kinetics and localization of dye accumulation in the neovascular cornea of rats after systemic administration and the development of vascular injury induced by subsequent laser irradiation, compared to those in the normal iris. Under a fluorescence microscope, the neovascular cornea always exhibited more intense fluorescence than the iris between 0.5 and 4 hr after ATX-S10 administration, indicating the preferential deposit of dye in the former tissue. The fluorescence was found inside the vascular lumen at the earliest time period and thereafter in the vascular lining cells, interstitial tissue and infiltrating neutrophils until 6 hr. As observed using light and electron microscopy, laser irradiation performed 2.5 hr after ATX-S10 injection caused extensive vascular thrombosis with endothelial destruction, which persisted for at least 3 days. The proportion of thrombosed vessels at 6 hr after laser irradiation in the neovascular cornea (64+/-5%; n=3) was significantly (P<0.01) higher than that in the normal iris (44+/-8%; n=3). In the non-thrombosed vessels from heparinized rats, in which thrombosis-related ischemic effect was excluded, mitochondrial vacuolation was the pathologic change commonly seen in the endothelial cells, pericytes and neutrophils. Morphometric analysis revealed that the mitochondria of endothelial cells in the corneal new vessels were more severely injured than those in the iris vessels. The present results indicate that ATX-S10 is a potent photosensitizer which induces photodynamic occlusion particularly of new vessels probably due to the preferential biodistribution of dye in the neovascular tissue.
Department of Ophthalmology, Osaka City University Medical School, Osaka, Japan.
Y
Y
Gohto
A
A
Obana
K
K
Kaneda
T
T
Miki
D000818:Animals; D003315:Cornea / Q000378:metabolism* / Q000648:ultrastructure; D016510:Corneal Neovascularization / Q000378:metabolism* / Q000473:pathology; D004728:Endothelium, Corneal / Q000648:ultrastructure; D005456:Fluorescent Dyes / Q000493:pharmacokinetics*; D007498:Iris / Q000098:blood supply / Q000378:metabolism / Q000648:ultrastructure; D007834:Lasers / Q000009:adverse effects; D008297:Male; D008854:Microscopy, Electron; D008856:Microscopy, Fluorescence; D008928:Mitochondria / Q000648:ultrastructure; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000493:pharmacokinetics*; D011166:Porphyrins / Q000493:pharmacokinetics*; D051381:Rats; D017208:Rats, Wistar; D013927:Thrombosis / Q000209:etiology / Q000473:pathology
C115550:ATX-S10; D005456:Fluorescent Dyes; D017319:Photosensitizing Agents; D011166:Porphyrins