Inhibition of corneal neovascularization with plasmid pigment epithelium-derived factor (p-PEDF) delivered by synthetic amphiphile INTeraction-18 (SAINT-18) vector in an experimental model of rat corneal angiogenesis.
The use of Synthetic Amphiphile INTeraction-18 (SAINT-18) carrying plasmid pigment epithelium-derived factor (p-PEDF) as an anti-angiogenesis strategy to treat corneal neovascularization in a rat model was evaluated. Four partially dried forms (Group A: 0 microg, B: 0.1 microg, C: 1 microg, D: 10 microg) of a p-PEDF-SAINT-18 were prepared and implanted into the rat subconjunctival substantia propria 1.5 mm from the limbus at the temporal side. The 1 microg of plasmid-basic fibroblast growth factor--SAINT-18 (p-bFGF-SAINT-18) (1 microg) was prepared and implanted into the rat corneal stroma 1.5 mm from the limbus on the same side. Inhibition of neovascularization was observed and quantified from day 1 to day 60. PEDF (50-kDa) and bFGF (18-kDa) protein expression were analyzed by biomicroscopic examination, Western blot analysis, and immunohistochemistry. Gene expression in corneal and conjunctival tissue was observed as early as 3 days after gene transfer and stably lasted for over 3 months with minimal immune reaction. Subconjunctival injection of a highly efficient p-PEDF-SAINT-18 successfully inhibited corneal neovascularization. Successful gene expression of bFGF, PEDF and a mild immune response of HLA-DR were shown by immunohistochemistry staining. We concluded that SAINT-18 was capable of directly delivering genes to the ocular surface by way of subconjunctival injection, and delivered sustained, high levels of gene expression in vivo to inhibit angiogenesis.
Kuo
Chien-Neng
CN
Department of Ophthalmology, Chang Gung Memorial Hospital, Chiayi, Taiwan.
Yang
Lin-Cheng
LC
Yang
Cheng-Ta
CT
Lai
Chien-Hsiung
CH
Chen
Miao-Fen
MF
Chen
Chung-Yi
CY
Chen
Chi-Hung
CH
Wu
Pei-Chang
PC
Kou
Hsi-Kung
HK
Chen
Yung-Jen
YJ
Hung
Chia-Hui
CH
Tsai
Chong-Bin
CB
D000818:Animals; D015153:Blotting, Western; D003228:Conjunctiva / Q000378:metabolism*; D003315:Cornea / Q000098:blood supply* / Q000276:immunology / Q000378:metabolism*; D016510:Corneal Neovascularization / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D004195:Disease Models, Animal; D005136:Eye Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D005240:Feasibility Studies; D016222:Fibroblast Growth Factor 2 / Q000096:biosynthesis / Q000235:genetics; D015316:Genetic Therapy / Q000379:methods*; D006684:HLA-DR Antigens / Q000276:immunology; D007150:Immunohistochemistry; D007267:Injections; D008297:Male; D009414:Nerve Growth Factors / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D011726:Pyridinium Compounds / Q000276:immunology / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015843:Serpins / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D013997:Time Factors; D014162:Transfection; D000099174:Pigment Epithelium-Derived Factor
D005136:Eye Proteins; D016222:Fibroblast Growth Factor 2; D006684:HLA-DR Antigens; D009414:Nerve Growth Factors; D011726:Pyridinium Compounds; D015843:Serpins; D000099174:Pigment Epithelium-Derived Factor; C532953:1-methyl-4-(9-dioleyl)methylpyridinium