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Periocular injection of an adenoviral vector encoding pigment epithelium-derived factor inhibits choroidal neovascularization
- Source :
- Gene Therapy. 10:637-646
- Publication Year :
- 2003
- Publisher :
- Springer Science and Business Media LLC, 2003.
-
Abstract
- Gene transfer provides an exciting new approach for the treatment of retinal and choroidal diseases. Two areas of concern are the potential for vector-related toxicity and uncertainties associated with prolonged transgene expression. One way to address these concerns for transfer of genes encoding secreted proteins is to transduce cells on the outside of the eye, provided the gene product can gain access to the eye and have the desired effect. In this study, we investigated the feasibility of this approach. Periocular injection of an adenoviral vector encoding beta-galactosidase (AdLacZ.10) resulted in LacZ-stained cells throughout the orbit and around the eye. Compared to periocular injection of 5 x 10(9) particles of control vector, periocular injection of 5 x 10(9) or 1 x 10(9) particles of an adenoviral vector expressing pigment epithelium-derived factor (PEDF) regulated by a CMV promoter (AdPEDF.11) resulted in significantly elevated intraocular levels of PEDF and suppression of choroidal neovascularization. Periocularly injected recombinant PEDF was also found to diffuse through the sclera into the eye. Although similar experiments are needed in an animal with a human-sized eye, these data suggest that periocular gene transfer deserves consideration for the treatment of choroidal diseases.
- Subjects :
- Pathology
medicine.medical_specialty
genetic structures
Genetic enhancement
Genetic Vectors
Gene Expression
Biology
Eye
Adenoviridae
Injections
Viral vector
Neovascularization
Mice
chemistry.chemical_compound
PEDF
Genetics
medicine
Animals
Nerve Growth Factors
Eye Proteins
Molecular Biology
Serpins
Genetic transfer
Proteins
Retinal
Genetic Therapy
beta-Galactosidase
Choroidal Neovascularization
eye diseases
Sclera
Mice, Inbred C57BL
Choroidal neovascularization
medicine.anatomical_structure
chemistry
Models, Animal
Cancer research
Molecular Medicine
sense organs
medicine.symptom
Orbit
Subjects
Details
- ISSN :
- 14765462 and 09697128
- Volume :
- 10
- Database :
- OpenAIRE
- Journal :
- Gene Therapy
- Accession number :
- edsair.doi.dedup.....26df179cbc18628d69311f6b29bf36a8