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Optimizing Subretinal Bleb Formation for Visual Streak Involvement in a Porcine Model for Retinal Gene Therapy
IP. Seitz, T. Peters, F. Reichel, A. Bähr, H. Auch, J. Motlik, T. Ardan, J. Juhasova, Y. Nemesh, S. Juhás, N. Klymiuk, MD. Fischer
Jazyk angličtina Země Spojené státy americké
Typ dokumentu časopisecké články
NLK
Directory of Open Access Journals
od 2016
Free Medical Journals
od 1962
PubMed Central
od 2007
ROAD: Directory of Open Access Scholarly Resources
od 1977
PubMed
39466231
DOI
10.1167/iovs.65.12.41
Knihovny.cz E-zdroje
- MeSH
- genetická terapie * metody MeSH
- injekce nitrooční MeSH
- modely nemocí na zvířatech * MeSH
- prasata MeSH
- retina MeSH
- subretinální tekutina metabolismus MeSH
- Sus scrofa MeSH
- vitrektomie * metody MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
PURPOSE: Subretinal (SR) injection in porcine models is a promising avenue for preclinical evaluation of cell and gene therapies. Targeting of the subretinal fluid compartment (bleb) is critical to the procedure, especially if treatment of the cone-rich area centralis is required (i.e., visual streak [VS] in pigs). To our knowledge, this study is the first to investigate the influence of injection site placement on VS involvement in the pig eye. METHODS: We performed 23-gauge pars plana vitrectomy followed by SR injection in 41 eyes of 21 animals (Sus scrofa domesticus). In 27 eyes (65.9%), the injection site was placed superior to the VS, and in 14 eyes (34.1%) it was placed inferior to it. Using intraoperative imaging, blebs were classified based on their propagation behavior relative to the VS. RESULTS: In 79% of cases, blebs from inferior injection sites developed away from the VS, exhibiting a mean ± SEM vertical anisotropy (AP) of 0.67 ± 0.11. In contrast, blebs from superior injection sites tended to develop toward the VS with an AP of 1.27 ± 0.18 (P = 0.0070). Blebs developed away from the VS in only 41% of injections (P = 0.0212). Inferior blebs were orientated close to 0° (horizontal), whereas superior blebs displayed varied orientations with a mean angle of 56° (P = 0.0008). CONCLUSIONS: Bleb propagation was anisotropic (i.e., directionally biased) and dependent on injection site placement. Superior injection sites led to superior VS detachment. Morphological analysis suggested increased adhesion forces at the VS and superior vascular arcades. This study will aid the planning of surgeries for targeted subretinal delivery in pig models.
Center for Innovative Medical Models Ludwig Maximilians Universität München München Bayern Germany
Institute of Animal Physiology and Genetics Akademie věd České republiky Praha Czechia
University Eye Hospital Eberhard Karls Universität Tübingen Tübingen Baden Württemberg Germany
Citace poskytuje Crossref.org
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