Background: The eye possesses unique anatomical features that make it a valuable target
for gene therapy applications.
Objective: The aim of the current study was to compare transduction efficiency, safety and biodistribution
of four viral vectors following intravitreal injection.
Method: Adenovirus (AdV), Adeno-Associated Virus (AAV), Baculovirus (BV) and Lentivirus (LV)
vectors encoding Green Fluorescent Protein (GFP) were injected bilaterally intravitreally into adult
C57BL/6OlaHsd mice. Control mice received saline. Eyes and other organs were studied at multiple
time points from 3 days to 6 months. Immunohistochemical stainings with retinal cell markers were
performed to verify GFP-positive cells. Biodistribution in retina and various non-target tissues was
studied using a qPCR method. Inflammatory responses and toxicity were investigated from cryostat
eye sections and serum samples.
Results: AAV-injected eyes showed GFP expression both in inner and outer retinal cells from 7 days up
to 6 months. LV eyes showed long lasting transgene expression mostly in retinal pigment epithelium
whereas AdV transiently transduced mainly cells in the anterior chamber. In BV-injected eyes, GFP positivity
was very low. qPCR results showed that AdV, AAV and LV spread into the optic nerve, but were
below the detection limit in other organs. The strongest immune responses were evoked by intravitreal
injections of AdV and BV. The highest concentration of anti-GFP IgG was detected in the AdV-treated
group, whereas the AAV group showed the lowest concentration. Neither blood chemistry screen nor the
number of apoptotic cells showed any differences between the viral vector and saline injected groups.
Conclusion: Our findings show that intravitreal gene delivery is safe and feasible with AAV, AdV
and lentivirus vectors.