Targeted decorin gene therapy delivered with adeno-associated virus effectively retards corneal neovascularization in vivo

Autor: J. C. K. Tovey, Gregory S. Schultz, Ashish Tandon, John W. Cowden, Rajiv R. Mohan, Ajay Sharma
Rok vydání: 2011
Předmět:
Pathology
Decorin
lcsh:Medicine
Gene Expression
medicine.disease_cause
Biochemistry
Neovascularization
Cornea
0302 clinical medicine
lcsh:Science
Adeno-associated virus
Corneal epithelium
0303 health sciences
Multidisciplinary
Neovascularization
Pathologic

Animal Models
Gene Therapy
Dependovirus
Immunohistochemistry
3. Good health
medicine.anatomical_structure
Gene Targeting
Corneal Disorders
Medicine
Female
Rabbits
medicine.symptom
Tomography
Optical Coherence

Research Article
medicine.medical_specialty
Blotting
Western

Biology
Real-Time Polymerase Chain Reaction
03 medical and health sciences
PEDF
Model Organisms
medicine
Genetics
Animals
RNA
Messenger

030304 developmental biology
DNA Primers
Clinical Genetics
Base Sequence
lcsh:R
Proteins
Genetic Therapy
medicine.disease
Molecular biology
eye diseases
carbohydrates (lipids)
Ophthalmology
Small Molecules
Corneal neovascularization
030221 ophthalmology & optometry
lcsh:Q
sense organs
Gene Function
Immunostaining
Zdroj: PLoS ONE
PLoS ONE, Vol 6, Iss 10, p e26432 (2011)
ISSN: 1932-6203
Popis: Decorin, small leucine-rich proteoglycan, has been shown to modulate angiogenesis in nonocular tissues. This study tested a hypothesis that tissue-selective targeted decorin gene therapy delivered to the rabbit stroma with adeno-associated virus serotype 5 (AAV5) impedes corneal neovascularization (CNV) in vivo without significant side effects. An established rabbit CNV model was used. Targeted decorin gene therapy in the rabbit stroma was delivered with a single topical AAV5 titer (100 µl; 5×10(12) vg/ml) application onto the stroma for two minutes after removing corneal epithelium. The levels of CNV were examined with stereomicroscopy, H&E staining, lectin, collagen type IV, CD31 immunocytochemistry and CD31 immunoblotting. Real-time PCR quantified mRNA expression of pro- and anti-angiogenic genes. Corneal health in live animals was monitored with clinical, slit-lamp and optical coherence tomography biomicroscopic examinations. Selective decorin delivery into stroma showed significant 52% (p
Databáze: OpenAIRE