Suppression of retinal neovascularization by the NF-kappaB inhibitor pyrrolidine dithiocarbamate in mice.
OBJECTIVE
To evaluate the effect of pyrrolidine dithiocarbamate (PDTC), an inhibitor of nuclear factor kappaB (NF-kappaB), on retinal neovascularization in a murine model of ischemic retinopathy.


METHODS
One-week-old C57BL/6N mice were exposed to 75%+/-2% oxygen for 5 days and then were returned to room air to induce retinal neovascularization. After the return to room air, the left and right eyes were injected intravitreally with PDTC or a vehicle, respectively. Retinal neovascularization was examined by injecting fluorescein dextran and angiography after 5 days in room air and was quantitated histologically with a masked protocol. The effects of PDTC on NF-kappaB activation were evaluated by immunohistochemistry. To examine the toxicity of PDTC, the histologic change in the retina was examined by light and electron microscopy.


RESULTS
Retinal neovascularization in the eye injected with PDTC by intravitreal methods was reduced in 100% of animals compared with that apparent in the vehicle-treated eye. The inhibitory effect was dose-dependent, with a maximal inhibition of 39% (P < 0.01) at a dose of 1 nmole. The immunostaining intensity for NF-KB in the retina was reduced by PDTC injections. No side effects by PDTC in the retina were observed by light and electron microscopy.


CONCLUSIONS
NF-kappaB activation appears to be required for retinal angiogenesis, given that the administration of PDTC suppressed retinal neovascularization. PDTC may prove beneficial in the treatment of ischemic neovascular diseases such as diabetic retinopathy and retinal vein occlusion.
Yoshida
A
A
Department of Ophthalmology, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Yoshida
S
S
Ishibashi
T
T
Kuwano
M
M
Inomata
H
H
D000818:Animals; D000831:Animals, Newborn; D000975:Antioxidants / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005451:Fluorescein Angiography; D005654:Fundus Oculi; D000860:Hypoxia / Q000150:complications; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D011759:Pyrrolidines / Q000494:pharmacology*; D012160:Retina / Q000187:drug effects* / Q000473:pathology; D015861:Retinal Neovascularization / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D013859:Thiocarbamates / Q000494:pharmacology*
D000975:Antioxidants; D016328:NF-kappa B; D011759:Pyrrolidines; D013859:Thiocarbamates; C020972:pyrrolidine dithiocarbamic acid