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

IF 5 2区 医学 Q1 OPHTHALMOLOGY Investigative ophthalmology & visual science Pub Date : 2024-10-01 DOI:10.1167/iovs.65.12.41
Immanuel P Seitz, Tobias Peters, Felix Reichel, Andrea Bähr, Hanna Auch, Jan Motlik, Taras Ardan, Jana Juhasova, Yaroslav Nemesh, Stefan Juhás, Nikolai Klymiuk, Manuel Dominik Fischer
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Abstract

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.

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在猪视网膜基因治疗模型中优化视网膜下出血点的形成,以实现视觉条纹参与。
目的:在猪模型中进行视网膜下注射是对细胞和基因疗法进行临床前评估的一个很有前景的途径。瞄准视网膜下积液区(虹膜睫状体)对手术至关重要,尤其是在需要治疗富含视锥的中央区时(即猪的视觉条纹 [VS])。据我们所知,本研究是首次研究注射部位的位置对猪眼 VS 受累情况的影响:我们对 21 头猪的 41 只眼睛进行了 23 号玻璃体旁切除术,然后注射了 SR。27只眼睛(65.9%)的注射部位位于VS上方,14只眼睛(34.1%)的注射部位位于VS下方。通过术中成像,根据出血点相对于 VS 的传播行为对其进行分类:在79%的病例中,来自下注射点的出血点远离VS发展,显示出平均±SEM垂直各向异性(AP)为0.67±0.11。相反,上注射点的出血点倾向于向 VS 方向发展,AP 为 1.27 ± 0.18(P = 0.0070)。仅有 41% 的注射部位出血点远离 VS(P = 0.0212)。下出血点的方向接近 0°(水平),而上出血点的方向各不相同,平均角度为 56°(P = 0.0008):出血点的传播是各向异性的(即方向性偏差),并取决于注射部位的位置。注射部位越靠上,VS脱离越靠上。形态学分析表明,VS和上血管弧的粘附力增加。这项研究将有助于规划猪模型视网膜下定向注射的手术。
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来源期刊
CiteScore
6.90
自引率
4.50%
发文量
339
审稿时长
1 months
期刊介绍: Investigative Ophthalmology & Visual Science (IOVS), published as ready online, is a peer-reviewed academic journal of the Association for Research in Vision and Ophthalmology (ARVO). IOVS features original research, mostly pertaining to clinical and laboratory ophthalmology and vision research in general.
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