P2.52. FUNCTIONAL INTRODUCTION OF RABIES VIRUS TO HEALTHY AND DEGENERATED RETINA
Anna Galińska1,2, Jagoda Płaczkiewicz1,2, Karolina Saran1,2, Milena Gumkowska1,2, Andrzej T. Foik1,2
1 International Centre for Translational Eye Research, Institute of Physical Chemistry PAS, Skierniewicka 10a, 01-230 Warsaw, Poland
2 Institute of Physical Chemistry, Polish Academy of Sciences, Kasprzaka 44/52, 01-224 Warsaw, Poland
INTRODUCTION: The Rabies virus (RV) is a (-)RNA rhabdovirus, known for its ability to infect neurons via retrograde transport. In neurons infected with a modified RV, we observed high expression of protein-coding genes. However, there is currently no definitive evidence demonstrating the effectiveness of the G-deleted rabies virus (RVΔG) in infecting retinal cells.
AIM(S): We tested whether RVΔG can infect various types of retinal cells in the healthy and the degenerated retinas, and whether there are differences between the infection of cells in those types of retinas.
METHOD(S): We injected RVΔG carrying a fluorescent protein into the eyes of wild-type and RhoP23H/P23H mice via subretinal delivery. Infected cell types were identified through immunostained retinal whole mounts and cross-sections. Functional vision reactivation in degenerated retinas was assessed using optogenetic recordings after injections of RVΔG carrying blue- and yellow-light-sensitive opsins.
RESULTS: We found that RVΔG is capable of infecting a broad spectrum of retinal cell types, including RGCs. Infection rates were comparable between healthy and degenerated retinas, with no significant differences observed. In optogenetic recordings, light-evoked responses were detected in a 3-month-old RhoP23H/P23H mouse 14–16 days post-infection, indicating functional reactivation of the degenerated retina.
CONCLUSIONS: Our findings suggest that RVΔG is an effective tool for delivering genetic cargo into retinal cells, offering valuable insights into retinal connectivity. Additionally, it shows strong potential for targeting and delivering cargo to cells that are retrogradely connected within the retina.
FINANCIAL SUPPORT: Funded by the National Science Centre, Poland, under project no. 2019/32/E/NZ5/00434 within Sonata bis 9 call and project no. 2020/39/D/NZ4/01881 within Sonata 16 call.
The International Centre for Translational Eye Research (FENG.02.01-IP.05-T005/23) project is carried out within the International Research Agendas programme of the Foundation for Polish Science co-financed by the European Union under the European Regional Development Fund.