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 |
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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 |
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