Anterior chamber tropism and systemic biodistribution of recombinant adeno-associated virus (rAAV) serotypes following intracameral injection.

Anterior segment disorders affecting the cornea and trabecular meshwork, such as endothelial dystrophies and open-angle glaucoma, cause approximately 12% of global blindness. Several such diseases, particularly those caused by single gene mutations, may be amenable to gene therapy or editing and as such it is critical to understand the tropism of recombinant adeno-associated virus (rAAV)-mediated vectors following intracameral injection in order to target affected tissues efficiently and safely. In this study, we investigate the tropism and systemic biodistribution of several rAAV serotypes (rAAV2/2, 2/2 [MAX], 2/2 [7m8], 2/5, 2/6, 2/7, 2/8, and 2/9) expressing a green fluorescent protein (GFP) reporter following intracameral injection in wild-type C57BL/6 J mice. Using a combination of in vivo fluorescence imaging and post-mortem histology, we demonstrate that rAAV serotypes differentially target the iris (rAAV2/2 and related capsid mutants), corneal stroma (rAAV2/7 and rAAV2/8) and endothelium (rAAV2/5), while virions remain largely contained within the injected eye.