Inhibition of chemical cautery-induced corneal neovascularization by topical pigment epithelium-derived factor eyedrops.
OBJECTIVE
To evaluate the effect of topically administered pigment epithelium-derived factor (PEDF) on experimentally induced corneal neovascularization (NV) in a rat model.


METHODS
Corneal chemical cauterization was induced in the left eye by using silver nitrate sticks in 160 anesthetized male Sprague-Dawley rats. The rats were randomly assigned to 4 groups with 40 rats each for topical administration of recombinant PEDF, chloramphenicol, chondroitin sulfate, and normal saline (as control). At different intervals (3, 10, 15, and 30 days) of the treatment, rats were euthanized and the corneas removed for immunohistochemistry and Western blot analyses to measure expression levels of PEDF, vascular endothelial growth factor (VEGF), and CD34, an endothelial maker. The right eyes were used as normal control.


RESULTS
There were high levels of PEDF expression and low levels of VEGF and CD34 in the normal cornea. VEGF and CD34 levels were significantly induced by chemical cauterization in the groups treated with chloramphenicol, chondroitin sulfate, and normal saline, demonstrating corneal NV. The VEGF and CD34 levels reached a plateau in the cornea on the 10th day after cauterization and remained at high levels thereafter. In contrast, the PEDF treatment prevented the overexpression of VEGF and CD34 induced by the cauterization.


CONCLUSIONS
PEDF downregulates VEGF expression and inhibits corneal NV induced by chemical cauterization. The results suggested that PEDF has therapeutic potential for corneal neovascular diseases.
Department of Ophthalmology, Children's Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Ji
J
Jin
Jian-Xing
JX
Ma
Ming
M
Guan
Ke
K
Yao
D000287:Administration, Topical; D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism; D015153:Blotting, Western; D002425:Cautery; D002701:Chloramphenicol / Q000008:administration & dosage; D002809:Chondroitin Sulfates / Q000008:administration & dosage; D016510:Corneal Neovascularization / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D004195:Disease Models, Animal; D005136:Eye Proteins / Q000008:administration & dosage*; D007150:Immunohistochemistry; D008297:Male; D009414:Nerve Growth Factors / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000008:administration & dosage*; D015843:Serpins / Q000008:administration & dosage*; D012835:Silver Nitrate / Q000633:toxicity; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D000099174:Pigment Epithelium-Derived Factor
D018952:Antigens, CD34; D002701:Chloramphenicol; D002809:Chondroitin Sulfates; D005136:Eye Proteins; D009414:Nerve Growth Factors; D011994:Recombinant Proteins; D015843:Serpins; D012835:Silver Nitrate; D042461:Vascular Endothelial Growth Factor A; D000099174:Pigment Epithelium-Derived Factor; C467498:vascular endothelial growth factor A, rat