[Transfer of endostatin gene for inhibition of retinal angiogenesis in mice].
OBJECTIVE
To evaluate the effect of liposome mediated plasmids encoding endostatin (ES) injected into the vitreous to inhibit experimental retinal neovascularization.


METHODS
Cationic liposome mediated ES expression plasmid PCDNA(3)-ES was constructed. One-week-old C57Bl/6N mice were exposed to (75 +/- 2)% oxygen for 5 days, then returned to the room air to induce retinal neovascularization. Cationic liposome mediated ES complex (2 microl) was injected into the vitreous in the treatment group. PBS 2 microl or liposome with carrier DNA complex were injected in the control group. The ES protein expression in the retina was tested with immunohistological methods at 1, 3, 7 and 14 days after injection. Retinal neovascularization was evaluated by angiography with injection of fluorescein dextran and quantification of neovascular proliferative retinopathy after 5 days in room air. To examine the toxicity of the liposome and plasmid PCDNA(3)-ES complex, the histological changes in the retina were examined by light and electron microscopy.


RESULTS
ES protein was expressed in the retina 24 hours after injection. Most of them presented in the retinal ganglion layer. This could last for 2 weeks at least. Retina of the PBS-injected eyes of retinal neovascular animal model showed prominent neovascular tuft and fluorescein leakage. Fewer neovascular tufts could be seen after ES injection. Retinal neovascularization in the eyes injected with ES plasmids complex was reduced as compared with the control group. No side effect on the retina was observed by light and electron microscopy.


CONCLUSIONS
Liposome mediated plasmids encoding ES can be transferred to retinal cells by vitreous injection and can suppress retinal neovascularization, no side or toxic effects are presented in the retina. Further studies should be done to improve the treatment results.
Wang
Wei
W
Shandong Provincal Key Leb of Ophthalmology, Shandong Eye Institute, Qingdao 266071, China.
Xie
Li-xin
LX
Dong
Xiao-guang
XG
Zang
Xin-jie
XJ
D020533:Angiogenesis Inhibitors / Q000235:genetics* / Q000494:pharmacology; D000818:Animals; D043169:Endostatins / Q000235:genetics* / Q000494:pharmacology; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D008081:Liposomes; D051379:Mice; D012160:Retina / Q000473:pathology; D015861:Retinal Neovascularization / Q000473:pathology / Q000628:therapy*
D020533:Angiogenesis Inhibitors; D043169:Endostatins; D008081:Liposomes