Abstract
Purpose :
While robust methods exist for suprachoroidal space (SCS) delivery in larger animals (e.g. rabbits, primates), reliable SCS injection in rodents has yet to be achieved given their substantially smaller eye size. We hypothesize that liquid formulations can be successfully deposited in the SCS when 1) a microneedle injector is properly scaled to ascertain the complete and precise penetration of the needle length across the extremely thin rodents’ sclera, and 2) the eye is stabilized while injecting to reduce the probability of failure due to stochastic movements.
Methods :
Glass microneedles were fabricated out of glass pipettes, tapering to a tip diameter of 110 µm. 3D-printing was utilized to fabricate different injector designs, and each design was tested to find the optimal configuration. Wistar rats (N=12) and guinea pigs (N=6) were each injected suprachoroidally in one eye with nanoparticle suspensions, while the contralateral eye remained naïve. A custom-made 3D-printed probe was constructed and used to secure the eye firmly in position while injecting. Fundoscopy, slit lamp examination and post-mortem analysis including histological and immunohistochemical staining were performed on all eyes post-procedure.
Results :
An optimum injector was achieved with design features fit for miniscule dimensions of rodents’ eyes and was used henceforth. Fundoscopy together with confocal imaging of the histology sections confirmed the targeted delivery of nanoparticles to the SCS in all eyes. The optimum microneedle length was found to be 160 ± 10 µm and 260 ± 10 µm for rats and guinea pigs, respectively. Immunohistochemistry and histopathological analysis further revealed no evidence of retinal/RPE abnormalities or choroidal complications in the injected eyes compared to the control eyes.
Conclusions :
The ability to reliably deliver to the SCS of rodents facilitates pre-clinical testing of a variety of novel therapeutics and accelerates the development of new ocular therapies. Rodents are an ideal model for pre-clinical investigations given their low cost and availability of various ocular disease models. Here, we highlight the ability of a robust microneedle delivery technique for SCS injection in rodents. The proposed method accomplished SCS delivery with 100% success rate in a simple, minimally-invasive procedure that takes less than one minute for each injection and requires no surgical microscope.
This is a 2021 ARVO Annual Meeting abstract.