title: Recombinant adeno-associated virus vector expressing angiostatin inhibits preretinal neovascularization in adult rats.
abstract: Clinically, preretinal neovascularization (PNV) induced by vessel occlusion is one of the leading causes to induce blindness. The present study was designed to determine if a recombinant adeno-associated viral vector expressing mouse angiostatin (rAAV-angiostatin) can inhibit experimental PNV in an adult Sprague-Dawley rat model. rAAV-angiostatin and rAAV-lacZ were delivered by intravitreal injections to the right and left eyes of rats. Transgenetic expression of angiostatin in the retina was determined by reverse-transcriptase polymerase chain reaction (RT-PCR). PNV was established by rose-bengal-assisted laser-induced retinal vein occlusion 21 days after the viral injections. The total number and sizes of the neovascular tufts were analyzed 14 days after venous occlusion using retinal flat mount by fluorescein-isothiocyanate-dextran angiography. Electroretinograms (ERGs) were recorded to study any possibility of retinal toxicity of rAAV-angiostatin 3 months after the injections. Angiostatin gene expression in the retina was detectable by RT-PCR, and ERG analysis showed no reduction of b-waves in the rAAV-angiostatin-injected eyes. The number and size of neovascular tufts were significantly lower in rAAV-angiostatin-injected eyes (p = 0.001) than controls. These findings indicated that rAAV-angiostatin successfully suppressed experimental PNV, and no retinal toxicity of the rAAV-angiostatin injection was observed according to ERG recordings.
authors.affiliation: Department of Ophthalmology, Chang-Gung Memorial Hospital, Taoyuan, Taiwan.
authors.forename: Chi-Chun
authors.initials: CC
authors.lastname: Lai
authors.forename: Wei-Chi
authors.initials: WC
authors.lastname: Wu
authors.forename: Show-Li
authors.initials: SL
authors.lastname: Chen
authors.forename: Ming-Hui
authors.initials: MH
authors.lastname: Sun
authors.forename: Xiao
authors.initials: X
authors.lastname: Xiao
authors.forename: Lih
authors.initials: L
authors.lastname: Ma
authors.forename: Keng-Kuo
authors.initials: KK
authors.lastname: Lin
authors.forename: Yeou-Ping
authors.initials: YP
authors.lastname: Tsao
mesh_terms: D043168:Angiostatins / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D003673:Defective Viruses; D000229:Dependovirus / Q000235:genetics*; D004195:Disease Models, Animal; D004596:Electroretinography; D005451:Fluorescein Angiography; D015870:Gene Expression; D015316:Genetic Therapy; D005822:Genetic Vectors; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015861:Retinal Neovascularization / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D012170:Retinal Vein Occlusion / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019076:Transgenes
chemical_list: D012333:RNA, Messenger; D043168:Angiostatins