title: Periocular gene transfer of pigment epithelium-derived factor inhibits choroidal neovascularization in a human-sized eye.
abstract: Gene transfer provides a potential way to achieve sustained delivery of therapeutic proteins to the eye. Studies in rodents have suggested that periocular injection of adenoviral vectors containing expression cassettes for antiangiogenic proteins results in high intraocular levels of the proteins and suppression of choroidal neovascularization (CNV). However, the differences in size and scleral thickness between mouse and human eyes make it difficult to ascertain if periocular gene transfer is a feasible approach for treating human choroidal diseases. To address this issue, we tested the effect of periocular injection of an expression cassette for pigment epithelium-derived factor (PEDF) packaged in adenoviral vector (AdPEDF.11) in a CNV model in pigs, which have eyes that are very similar to humans in size and scleral thickness. Periocular injection of beta-galactosidase (AdLacZ.11) resulted in prominent transduction of periocular tissues, as was seen in mice. Periocular injection of AdPEDF.11 caused increased levels of PEDF in the choroid and significantly reduced the amount of CNV at rupture sites in Bruch's membrane. These data suggest that periocular gene transfer may be feasible for treatment of human choroidal diseases.
authors.affiliation: The Department of Ophthalmology, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA.
authors.forename: Yoshitsugu
authors.initials: Y
authors.lastname: Saishin
authors.forename: Raquel Lima
authors.initials: RL
authors.lastname: Silva
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Saishin
authors.forename: Shu
authors.initials: S
authors.lastname: Kachi
authors.forename: Sadia
authors.initials: S
authors.lastname: Aslam
authors.forename: Yuan Yuan
authors.initials: YY
authors.lastname: Gong
authors.forename: Hong
authors.initials: H
authors.lastname: Lai
authors.forename: Miguel
authors.initials: M
authors.lastname: Carrion
authors.forename: Brent
authors.initials: B
authors.lastname: Harris
authors.forename: Melissa
authors.initials: M
authors.lastname: Hamilton
authors.forename: Lisa
authors.initials: L
authors.lastname: Wei
authors.forename: Peter A
authors.initials: PA
authors.lastname: Campochiaro
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D016570:Bruch Membrane / Q000473:pathology; D020256:Choroidal Neovascularization / Q000473:pathology / Q000628:therapy*; D005136:Eye Proteins / Q000235:genetics* / Q000378:metabolism / Q000494:pharmacology; D005260:Female; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods; D005822:Genetic Vectors / Q000008:administration & dosage / Q000235:genetics / Q000494:pharmacology; D006801:Humans; D015552:Injections, Intralesional / Q000379:methods; D009414:Nerve Growth Factors / Q000235:genetics* / Q000378:metabolism / Q000494:pharmacology; D009929:Organ Size; D015843:Serpins / Q000235:genetics* / Q000378:metabolism / Q000494:pharmacology; D013552:Swine; D000099174:Pigment Epithelium-Derived Factor
chemical_list: D005136:Eye Proteins; D009414:Nerve Growth Factors; D015843:Serpins; D000099174:Pigment Epithelium-Derived Factor