Optimizing Subretinal Bleb Formation for Visual Streak Involvement in a Porcine Model for Retinal Gene Therapy.

Autor:	Seitz IP; University Eye Hospital, Eberhard-Karls-Universität Tübingen, Tübingen, Baden-Württemberg, Germany., Peters T; University Eye Hospital, Eberhard-Karls-Universität Tübingen, Tübingen, Baden-Württemberg, Germany., Reichel F; University Eye Hospital, Eberhard-Karls-Universität Tübingen, Tübingen, Baden-Württemberg, Germany.; Oxford University Hospitals NHS Foundation Trust, Oxford Eye Hospital, Oxford, Oxfordshire, United Kingdom., Bähr A; Medical Department I, Cardiology, Angiology, Pneumology, Klinikum rechts der Isar, Technische Universität München, München, Bayern, Germany.; Center for Innovative Medical Models, Ludwig-Maximilians-Universität München, München, Bayern, Germany., Auch H; Medical Department I, Cardiology, Angiology, Pneumology, Klinikum rechts der Isar, Technische Universität München, München, Bayern, Germany.; Center for Innovative Medical Models, Ludwig-Maximilians-Universität München, München, Bayern, Germany., Motlik J; Institute of Animal Physiology and Genetics, Akademie věd České republiky, Praha, Czechia., Ardan T; Institute of Animal Physiology and Genetics, Akademie věd České republiky, Praha, Czechia., Juhasova J; Institute of Animal Physiology and Genetics, Akademie věd České republiky, Praha, Czechia., Nemesh Y; Institute of Animal Physiology and Genetics, Akademie věd České republiky, Praha, Czechia., Juhás S; Institute of Animal Physiology and Genetics, Akademie věd České republiky, Praha, Czechia., Klymiuk N; Medical Department I, Cardiology, Angiology, Pneumology, Klinikum rechts der Isar, Technische Universität München, München, Bayern, Germany.; Center for Innovative Medical Models, Ludwig-Maximilians-Universität München, München, Bayern, Germany., Fischer MD; University Eye Hospital, Eberhard-Karls-Universität Tübingen, Tübingen, Baden-Württemberg, Germany.; Oxford University Hospitals NHS Foundation Trust, Oxford Eye Hospital, Oxford, Oxfordshire, United Kingdom.; Nuffield Department of Clinical Neurosciences, University of Oxford, The John Radcliffe Hospital, Oxford, United Kingdom.
Jazyk:	angličtina
Zdroj:	Investigative ophthalmology & visual science [Invest Ophthalmol Vis Sci] 2024 Oct 01; Vol. 65 (12), pp. 41.
DOI:	10.1167/iovs.65.12.41
Abstrakt:	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.
Databáze:	MEDLINE
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