Subretinal Injection Volume Correlates to Persistent Outer Retinal Thinning in the Pig Eye

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F67985904%3A_____%2F25%3A00642524" target="_blank" >RIV/67985904:_____/25:00642524 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216208:11310/25:10505854

Výsledek na webu

<a href="https://iovs.arvojournals.org/article.aspx?articleid=2811074" target="_blank" >https://iovs.arvojournals.org/article.aspx?articleid=2811074</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1167/iovs.66.14.27" target="_blank" >10.1167/iovs.66.14.27</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Subretinal Injection Volume Correlates to Persistent Outer Retinal Thinning in the Pig Eye

Popis výsledku v původním jazyce

PURPOSE. Transgenic pig models are a valuable model for preclinical testing of gene and cell therapies. Subretinal injection (SRI) is a common drug delivery method but has been associated with retinal thinning and atrophy. This study examined whether SRI volume correlates with retinal thinning in the pig eye and compared the effects of balanced salt solution (BSS) and adeno-associated virus (AAV) injections. METHODS. Ten eyes from five transgenic pigs were included in this study. Eight eyes received escalating subretinal injection volumes (SRVs) (50, 100, 150, and 200 mu L) of either BSS or AAV [5 x 10(11 )vg/mL], targeting the cone-rich area centralis of the pig eye. After six months, outer retinal thickness inside versus outside the bleb area (AORT) was quantified using optical coherence tomography (OCT). Histology was performed to confirm OCT findings. RESULTS. Treated eyes showed clinically relevant (-21.5 +/- 2.7 mu m) outer retinal thinning inside the bleb area (P = 0.0001). A strong, statistically significant, linear correlation (R-2 = 0.73 P = 0.0068) was found between SRV and ORT loss. There was a 1 mu m loss of ORT for every 9 mu L of SRV. ORT loss was similar between AAV and BSS, except at the highest volume (200 mu L, 1 x 10(11) vg), where greater thinning occurred with AAV over BSS (A11 mu m). CONCLUSIONS. This study supports the notion that SRV could be an independent factor in development of outer retinal thinning in the pig eye. Modifying surgical technique to favor the placement of multiple smaller blebs of <100 mu L might mitigate retinal thinning because of volumetric stress and enhance the preclinical safety profile of investigational therapies.

Název v anglickém jazyce

Subretinal Injection Volume Correlates to Persistent Outer Retinal Thinning in the Pig Eye

Popis výsledku anglicky

PURPOSE. Transgenic pig models are a valuable model for preclinical testing of gene and cell therapies. Subretinal injection (SRI) is a common drug delivery method but has been associated with retinal thinning and atrophy. This study examined whether SRI volume correlates with retinal thinning in the pig eye and compared the effects of balanced salt solution (BSS) and adeno-associated virus (AAV) injections. METHODS. Ten eyes from five transgenic pigs were included in this study. Eight eyes received escalating subretinal injection volumes (SRVs) (50, 100, 150, and 200 mu L) of either BSS or AAV [5 x 10(11 )vg/mL], targeting the cone-rich area centralis of the pig eye. After six months, outer retinal thickness inside versus outside the bleb area (AORT) was quantified using optical coherence tomography (OCT). Histology was performed to confirm OCT findings. RESULTS. Treated eyes showed clinically relevant (-21.5 +/- 2.7 mu m) outer retinal thinning inside the bleb area (P = 0.0001). A strong, statistically significant, linear correlation (R-2 = 0.73 P = 0.0068) was found between SRV and ORT loss. There was a 1 mu m loss of ORT for every 9 mu L of SRV. ORT loss was similar between AAV and BSS, except at the highest volume (200 mu L, 1 x 10(11) vg), where greater thinning occurred with AAV over BSS (A11 mu m). CONCLUSIONS. This study supports the notion that SRV could be an independent factor in development of outer retinal thinning in the pig eye. Modifying surgical technique to favor the placement of multiple smaller blebs of <100 mu L might mitigate retinal thinning because of volumetric stress and enhance the preclinical safety profile of investigational therapies.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30103 - Neurosciences (including psychophysiology)

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

2025

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

66

Číslo periodika v rámci svazku

14

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

9

Strana od-do

27

Kód UT WoS článku

001622822500005

EID výsledku v databázi Scopus

2-s2.0-105021544885