Six-Month In Vivo Safety Profiling of Topical Ocular AAV5-Decorin Gene Transfer.

Autor:	Mohan RR; Harry S. Truman Memorial Veterans' Hospital, Columbia, Missouri, USA.; One-Health Vision Research Program, Departments of Veterinary Medicine & Surgery and Biomedical Sciences, College of Veterinary Medicine, University of Missouri, Columbia, MO, USA.; Mason Eye Institute, School of Medicine, University of Missouri, Columbia, Missouri, USA., Balne PK; Harry S. Truman Memorial Veterans' Hospital, Columbia, Missouri, USA.; One-Health Vision Research Program, Departments of Veterinary Medicine & Surgery and Biomedical Sciences, College of Veterinary Medicine, University of Missouri, Columbia, MO, USA., Muayad MS; Harry S. Truman Memorial Veterans' Hospital, Columbia, Missouri, USA.; One-Health Vision Research Program, Departments of Veterinary Medicine & Surgery and Biomedical Sciences, College of Veterinary Medicine, University of Missouri, Columbia, MO, USA., Tripathi R; Harry S. Truman Memorial Veterans' Hospital, Columbia, Missouri, USA.; One-Health Vision Research Program, Departments of Veterinary Medicine & Surgery and Biomedical Sciences, College of Veterinary Medicine, University of Missouri, Columbia, MO, USA., Sinha NR; Harry S. Truman Memorial Veterans' Hospital, Columbia, Missouri, USA.; One-Health Vision Research Program, Departments of Veterinary Medicine & Surgery and Biomedical Sciences, College of Veterinary Medicine, University of Missouri, Columbia, MO, USA., Gupta S; Harry S. Truman Memorial Veterans' Hospital, Columbia, Missouri, USA.; One-Health Vision Research Program, Departments of Veterinary Medicine & Surgery and Biomedical Sciences, College of Veterinary Medicine, University of Missouri, Columbia, MO, USA., An JA; Harry S. Truman Memorial Veterans' Hospital, Columbia, Missouri, USA.; Mason Eye Institute, School of Medicine, University of Missouri, Columbia, Missouri, USA., Sinha PR; Harry S. Truman Memorial Veterans' Hospital, Columbia, Missouri, USA.; One-Health Vision Research Program, Departments of Veterinary Medicine & Surgery and Biomedical Sciences, College of Veterinary Medicine, University of Missouri, Columbia, MO, USA., Hesemann NP; Harry S. Truman Memorial Veterans' Hospital, Columbia, Missouri, USA.; One-Health Vision Research Program, Departments of Veterinary Medicine & Surgery and Biomedical Sciences, College of Veterinary Medicine, University of Missouri, Columbia, MO, USA.
Jazyk:	angličtina
Zdroj:	Translational vision science & technology [Transl Vis Sci Technol] 2021 Aug 12; Vol. 10 (10), pp. 5.
DOI:	10.1167/tvst.10.10.5
Abstrakt:	Purpose: A significant remission of corneal fibrosis and neovascularization in rabbit eye in vivo was observed from a tissue-selective localized adeno-associated virus (AAV)5-Decorin (Dcn) gene therapy. This study sought to investigate 6-month toxicity profiling of this gene therapy for the eye in vivo using a rabbit model. Methods: A small epithelial scrape followed by corneal drying was performed unilaterally in 12 rabbit eyes and either AAV5-Dcn (n = 6) or naked vector (n = 6) was delivered topically using a cloning cylinder technique. Contralateral eyes served as naïve control (n = 6). Safety and tolerability measurements in live rabbits were performed periodically until month 6 using multimodel clinical ophthalmic imaging tools-a slit lamp, stereomicroscope, and HRT3-RCM in vivo confocal microscope. Thereafter, corneas were excised and subjected to hematoxylin and eosin staining, Mason trichome staining, propidium iodide nuclear staining, and quantitative real-time polymerase chain reaction analyses. Results: Clinical eye examinations based on the modified Hackett-McDonald ocular scoring system, and in vivo confocal imaging of the cornea showed no signs of ocular toxicity in rabbit eyes given AAV5-Dcn gene transfer vs control eyes (P > 0.05) through 6 months after treatment. The histologic and molecular analyses showed no significant differences in AAV5-Dcn vs AAV naked or naïve control groups (P > 0.05) and were in accordance with the masked clinical ophthalmic observations showing no abnormalities. Conclusions: Topical tissue-targeted localized AAV5-Dcn gene therapy seems to be safe and nontoxic to the rabbit eye in vivo. Translational Relevance: AAV5-Dcn gene therapy has the potential to treat corneal fibrosis and neovascularization in vivo safely without significant ocular toxicity.
Databáze:	MEDLINE
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