Effect of irradiation on neovascularization in rat skinfold chambers: implications for clinical trials of low-dose radiotherapy for wet-type age-related macular degeneration.
OBJECTIVE
Wet-type age-related macular degeneration is a refractory eye disease that involves choroidal neovascularization. Randomized controlled trials of low-dose radiotherapy for this disease performed in Japan showed that, at 12 months of follow-up, visual acuity was significantly well preserved and the neovascular membrane size decreased. Because understanding the effect of irradiation on new vascular networks is an important prerequisite for clinical trials, we used a rat skinfold chamber technique to investigate X-ray-induced changes in neovasculature microcirculation.


METHODS
Neovascularization was induced in rat skinfold chambers via polyvinyl chloride resin plates. Neovessels were irradiated in a single 10-Gy dose, after which, changes in vascular density, blood velocity, tissue blood flow, and interstitial fluid pressure (IFP), were measured.


RESULTS
Vascular density, tissue blood flow, and IFP measurements in resin-induced inflammatory tissue were much higher than those measurements in normal tissue. Although overall blood velocity was low and sluggish or blood-flow stasis occurred in the neovascular network, after a single 10-Gy dose of radiation, the velocity increased, stasis improved markedly, and many dilated vessels narrowed. Thereafter, vascular density, blood flow, and IFP significantly decreased and approached normal values.


CONCLUSIONS
These findings may help explain clinical results related to radiotherapy-induced changes in neovascular membranes in age-related macular degeneration. Both vascular morphology and vascular function in inflammatory tissue returned to normal, without vessel destruction, after an appropriate radiation dose.
Hori
Katsuyoshi
K
Department of Vascular Biology, Division of Cancer Control, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan. k-hori@idac.tohoku.ac.jp
Saito
Sachiko
S
Tamai
Makoto
M
D000818:Animals; D001783:Blood Flow Velocity / Q000528:radiation effects; D020256:Choroidal Neovascularization / Q000209:etiology / Q000473:pathology / Q000532:radiotherapy*; D045604:Extracellular Fluid / Q000502:physiology; D008268:Macular Degeneration / Q000473:pathology / Q000532:radiotherapy*; D008297:Male; D011143:Polyvinyl Chloride; D051381:Rats; D012039:Regional Blood Flow / Q000528:radiation effects; D014792:Visual Acuity / Q000528:radiation effects
D011143:Polyvinyl Chloride