Inhibitory effect of curcumin on corneal neovascularization in vitro and in vivo.
OBJECTIVE
To examine the effect of curcumin on the proliferation and the migration of human umbilical vein endothelial cells (HUVECs) and on the corneal neovascularization in the corneal alkaline burn rat model.


METHODS
HUVEC proliferation, migration, and apoptosis were examined after treatment with various concentrations of curcumin. The effect of curcumin on the activation of nuclear factor-kappaB (NF-kappaB) was measured by an electrophoretic mobility shift assay (EMSA) in vivo. Corneal neovascularization was induced in vivo by an alkaline burn of the cornea in Sprague-Dawley rats. After topical drug treatments with curcumin, vascular endothelial growth factor (VEGF) was evaluated in the corneal tissue by reverse transcription polymerase chain reaction and by immunohistochemistry. Corneal neovascularization was evaluated by slit-lamp biomicroscopy.


RESULTS
Curcumin at a concentration of 40 micromol/l for 24 h significantly inhibited the growth of HUVECs. The Boyden microchamber assay showed that curcumin dramatically inhibited the migration of HUVECs at a concentration of 40 micromol/l. When TUNEL assays were performed, the number of apoptotic cells increased after treated with curcumin. The EMSA revealed that curcumin inhibits the activation of NF-kappaB in HUVECs. The expression of VEGF in the corneal tissues was inhibited by curcumin on days 7 and 14 after alkaline burn.


CONCLUSIONS
Curcumin may be useful as an angiogenic inhibitor in the treatment of corneal diseases that show neovascularization.
Bian
Fang
F
Department of Ophthalmology, Union Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Zhang
Ming-Chang
MC
Zhu
Yun
Y
D000468:Alkalies; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000627:therapeutic use*; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D016510:Corneal Neovascularization / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D003474:Curcumin / Q000008:administration & dosage / Q000627:therapeutic use*; D004195:Disease Models, Animal; D024202:Electrophoretic Mobility Shift Assay; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008297:Male; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000473:pathology; D009883:Ophthalmic Solutions; D012313:RNA / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016896:Treatment Outcome; D014471:Umbilical Veins / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis / Q000235:genetics
D000468:Alkalies; D000894:Anti-Inflammatory Agents, Non-Steroidal; D009883:Ophthalmic Solutions; D042461:Vascular Endothelial Growth Factor A; D012313:RNA; D003474:Curcumin