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

Area of Science:

• Ophthalmology
• Preclinical Research
• Gene Therapy Delivery

Background:

• Transgenic pigs are vital for preclinical gene and cell therapy testing.
• Subretinal injection (SRI) is a common delivery method but can cause retinal thinning.
• Understanding SRI's impact on retinal structure is crucial for therapy development.

Purpose of the Study:

• To investigate the correlation between subretinal injection volume (SRV) and outer retinal thinning in pig eyes.
• To compare the effects of balanced salt solution (BSS) and adeno-associated virus (AAV) injections on retinal thickness.
• To assess the safety profile of subretinal injections in a preclinical model.

Main Methods:

• Ten transgenic pig eyes received escalating SRVs (50-200 µL) of BSS or AAV.
• Outer retinal thickness (ORT) changes were quantified using optical coherence tomography (OCT) six months post-injection.
• Histology confirmed OCT findings of retinal thinning within the bleb area.

Main Results:

• A significant linear correlation (R² = 0.73) was observed between SRV and outer retinal thinning (ORT loss).
• Each 9 µL increase in SRV resulted in approximately 1 µm of ORT loss.
• AAV injections at the highest volume (200 µL) showed greater thinning than BSS.

Conclusions:

• SRV is a significant factor contributing to outer retinal thinning in pig eyes.
• Minimizing SRV to <100 µL per bleb may reduce volumetric stress and retinal thinning.
• Optimizing surgical techniques can enhance the preclinical safety of gene and cell therapies delivered via SRI.