Inhibitory effect of YC-1, 3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole, on experimental choroidal neovascularization in rat.
OBJECTIVE
It was the aim of this study to evaluate the effects of YC-1, 3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole, one of the hypoxia-inducible factor 1 (HIF-1) inhibitors, on laser-induced choroidal neovascularization (CNV) in rats.


METHODS
Thirty female Brown Norway rats underwent laser photocoagulation to induce CNV. Twenty of them (treatment group) were treated with a single intravitreal injection of 5 microg YC-1, and the remaining 10 (control) were sham-treated with a single intravitreal injection of 2.5 mg/ml dimethyl sulfoxide 2 weeks after laser photocoagulation. The expression of HIF-1alpha and vascular endothelial growth factor (VEGF) in CNV was evaluated by immunofluorescence staining. Fluorescein angiography was performed 2 weeks before and 2 weeks after single intravitreal YC-1 (5 microg) and dimethyl sulfoxide (2.5 mg/ml) injection, grading fluorescein leakage from 0 to 3. The size of the CNV was measured on histologic sections.


RESULTS
Both HIF-1alpha and VEGF were expressed in CNV lesions in the control group 4 weeks after laser photocoagulation, whereas the expressions of HIF-1alpha and VEGF were not observed in the intravitreally YC-1-treated group. The mean fluorescein leakage score decreased from 2.56 +/- 0.49 to 0.79 +/- 0.71 in the intravitreally YC-1-injected group and from 2.62 +/- 0.49 to 1.58 +/- 0.60 in the control group. Sixty-eight (71.6%) out of 95 CNV lesions of intravitreally YC-1-treated eyes (71.4%) and 12 (21.8%) out of 55 lesions in DMSO-treated eyes showed a decreased fluorescein leakage score of 2 or more. The mean difference of fluorescein leakage scores between the intravitreally YC-1-treated group and the control group was significant (p = 0.004). The mean thickness of the CNV lesions in the intravitreally YC-1-treated group (27.30 +/- 6.47 microm) was smaller than that of the control group (64.36 +/- 8.26 microm, p < 0.001). There was no ocular inflammation, retina hemorrhage or systemic toxicity induced by YC-1 treatment.


CONCLUSIONS
These results suggest that YC-1 inhibits the HIF-1 expression after photocoagulation and suppresses the development of laser-induced CNV formation.
Song
Su-jeong
SJ
Department of Ophthalmology, College of Medicine and Medical Research Center, Seoul National University College, Seoul, Korea.
Chung
Hum
H
Yu
Hyeong Gon
HG
D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D020256:Choroidal Neovascularization / Q000175:diagnosis / Q000209:etiology* / Q000378:metabolism / Q000517:prevention & control*; D005260:Female; D005451:Fluorescein Angiography; D005455:Fluorescent Antibody Technique; D005654:Fundus Oculi; D051793:Hypoxia-Inducible Factor 1 / Q000037:antagonists & inhibitors*; D007191:Indazoles / Q000494:pharmacology*; D017075:Laser Coagulation; D051381:Rats; D011914:Rats, Inbred BN; D013194:Staining and Labeling; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors
D020533:Angiogenesis Inhibitors; D051793:Hypoxia-Inducible Factor 1; D007191:Indazoles; D042461:Vascular Endothelial Growth Factor A; C090937:3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole