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

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F67985904%3A_____%2F24%3A00600821" target="_blank" >RIV/67985904:_____/24:00600821 - isvavai.cz</a>

Výsledek na webu

<a href="https://iovs.arvojournals.org/article.aspx?articleid=2802174" target="_blank" >https://iovs.arvojournals.org/article.aspx?articleid=2802174</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1167/iovs.65.12.41" target="_blank" >10.1167/iovs.65.12.41</a>

Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

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 degrees (horizontal), whereas superior blebs displayed varied orientations with a mean angle of 56 degrees (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.

Název v anglickém jazyce

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

Popis výsledku anglicky

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 degrees (horizontal), whereas superior blebs displayed varied orientations with a mean angle of 56 degrees (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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30402 - Technologies involving the manipulation of cells, tissues, organs or the whole organism (assisted reproduction)

Projekt

<a href="/cs/project/EH22_008%2F0004562" target="_blank" >EH22_008/0004562: Excelentní výzkum v regenerativní medicíně</a><br>

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2024

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Investigative Ophthalmology and Visual Science

ISSN

0146-0404

e-ISSN

1552-5783

Svazek periodika

65

Číslo periodika v rámci svazku

12

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

6

Strana od-do

41

Kód UT WoS článku

001345204800003

EID výsledku v databázi Scopus

2-s2.0-85208001379