Suppression of retinal neovascularization by the NF-κB inhibitor pyrrolidine dithiocarbamate in mice

Ayako Yoshida, Shigeo Yoshida, Tatsuro Ishibashi, Michihiko Kuwano, Hajime Inomata

Research output: Contribution to journalArticle

122 Citations (Scopus)

Abstract

PURPOSE. To evaluate the effect of pyrrolidine dithiocarbamate (PDTC), an inhibitor of nuclear factor κB (NF-κB), 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- κB 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-κB 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-κB 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.

Original languageEnglish
Pages (from-to)1624-1629
Number of pages6
JournalInvestigative Ophthalmology and Visual Science
Volume40
Issue number7
Publication statusPublished - Jun 9 1999

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Retinal Neovascularization
Retina
Air
Electron Microscopy
pyrrolidine dithiocarbamic acid
Light
Retinal Vein Occlusion
Fluorescein Angiography
Diabetic Retinopathy
Inbred C57BL Mouse
Immunohistochemistry
Oxygen

All Science Journal Classification (ASJC) codes

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

Cite this

Suppression of retinal neovascularization by the NF-κB inhibitor pyrrolidine dithiocarbamate in mice. / Yoshida, Ayako; Yoshida, Shigeo; Ishibashi, Tatsuro; Kuwano, Michihiko; Inomata, Hajime.

In: Investigative Ophthalmology and Visual Science, Vol. 40, No. 7, 09.06.1999, p. 1624-1629.

Research output: Contribution to journalArticle

Yoshida, Ayako ; Yoshida, Shigeo ; Ishibashi, Tatsuro ; Kuwano, Michihiko ; Inomata, Hajime. / Suppression of retinal neovascularization by the NF-κB inhibitor pyrrolidine dithiocarbamate in mice. In: Investigative Ophthalmology and Visual Science. 1999 ; Vol. 40, No. 7. pp. 1624-1629.
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N2 - PURPOSE. To evaluate the effect of pyrrolidine dithiocarbamate (PDTC), an inhibitor of nuclear factor κB (NF-κB), 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- κB 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-κB 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-κB 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.

AB - PURPOSE. To evaluate the effect of pyrrolidine dithiocarbamate (PDTC), an inhibitor of nuclear factor κB (NF-κB), 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- κB 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-κB 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-κB 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.

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