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G. C. Shih, M. G. Sternberg, S. D. Crish, E. M. Harth, D. J. Calkins; Nanoparticle Drug Delivery to Retinal Ganglion Cells in Glaucoma. Invest. Ophthalmol. Vis. Sci. 2010;51(13):3167. doi: https://doi.org/.
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The leading risk factor for glaucoma is age, but elevated IOP is the only modifiable risk factor and the major therapeutic target. Current pressure-reducing treatments in the form of topical agents often prove marginal because of difficulties with patient compliance. As well, topical application of neuroprotective agents is highly variable. Here we examined the feasibility of using nanoparticle-encapsulated agents administered intravitreally in mice with elevated ocular pressure.
We constructed a 53nm nanosponge (Reti-Nano) with encapsulated DiO to measure retinal deposition following intravitreal injection in C57BL/6 mice. RGC DiO uptake was quantified by counting phosphorylated heavy-chain neurofilament (SMI31)+ RGCs with and without DiO. To determine the efficacy of brimonidine-loaded nanosponges in lowering IOP, C57BL/6 mice underwent microbead injection into the anterior chamber of both eyes to induce IOP elevation. Mice then received a single intravitreal injection of brimonidine nanoparticles into one eye and PBS in the other. IOP was measured in both eyes up to 10 days post-injection.
The retina appeared normal after nanoparticle injection. Retinal DiO deposition increased 3-fold after 14 days and 8-fold after 28 days compared to baseline. About 40% of SMI31+ RGCs also contained DiO. Brimonidine nanoparticle treatment resulted in a reduction of elevated IOP to near baseline levels over the course of 10 days
Reti-Nano nanoparticles reached the retina, remained there for a period of weeks, and showed no obvious toxic effects. DiO uptake by RGCs indicates that the nanoparticles passed the inner limiting membrane, a major barrier to many therapeutic compounds. Together with the reduction of IOP by nanoparticle-encapsulated brimonidine, this data suggests intravitreal injections of therapeutically-loaded nanoparticles may be a long-term drug delivery system in glaucoma.
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