Histochemical Analysis to Investigate the Efficacy and Safety of Suprachoroidal Injection in Rodents Using Microneedles

Purpose: A new and attractive alternative to current injection techniques for treating severe ocular diseases is the administration of liquid pharmacotherapies to the eye’s suprachoroidal space (SCS). Development of novel pharmaceuticals to target the SCS, however, hinges on the ability to reliably perform SCS injections in animal disease models during pre-clinical trials. Pioneered in larger animals, SCS delivery has yet to be achieved in rodents due to their smaller eye size. We hypothesize that a precisely scaled glass microneedle can be used to penetrate across the sclera and successfully and safely deliver liquid formulation to the rodent’s SCS.

Methods: Wistar rats (N=10) and guinea pigs (N=4) were injected with fluorescent suspensions to the SCS in one eye using the precisely scaled microneedle. In-vivo bright field and fluorescent fundoscopy were performed on all eyes pre- and post-procedure to view the back of the eye and assess SCS delivery. Samples were fixed and sectioned following a cryosectioning protocol post-mortem. Frozen sections were stained with either Hematoxylin and Eosin (H&E) or the Carstairs’ method, followed by Hoechst 33258 counterstain to visualize the retinal layers. They were then imaged via confocal microscopy.

Results: Both fundus and confocal images of the stained ocular sections confirmed the successful and targeted delivery of fluorescent particles to the SCS in all injected eyes. H&E stained sections showed no evidence of retinal complications near the injection site or optic nerve when compared to control eyes. No bleeding or abnormal structural disruption was observed in the Carstairs’ stained samples.

Conclusion: This study demonstrates efficacious and safe liquid delivery to the SCS in rodents using microneedles. Rodents are optimal for pre-clinical research due to their high availability, low cost, and the breadth of ocular diseases they can model. The ability to deliver therapeutics to rodents’ SCS enables more rapid and accessible pre-clinical testing of new pharmaceuticals to better treat ocular diseases.