Abstract
Purpose :
Retinal ganglion cell target therapy could be use in various ocular diseases, such as glaucoma, or macular degeneration. Nanoparticle-mediated drug delivery offers a promising avenue for targeted treatment, to retinal ganglion dells. This study explores an innovative therapeutic approach employing Arginylglycylaspartic Acid (RGD)-coated nanoparticles for enhanced adhesion to RGCs through integrin-mediated interactions.
Methods :
Monodispersed GNP coated with PVDF and RGDs were generated using modified Turkish methods in 1µm size. SEM was performed to evaluate the size and coating. Wild-type C57BL/6J mice, 4–8 weeks of age were anesthetized and underwent intravitreal injection of GNPs vs polymer coated nanoparticles, versus sham. Fundus photo, optical coherence tomography was taken and compared to pretreatment in same animal for 1 months post intravitreal injections. Hyper reflective particles were counted in the vitreous while length of hyper reflective particles on the retina were measured separately. Eye were enucleated, sectioned, and stained for imaging.
Results :
RGD-nanocompound observed to remain in mice eyes longer after injection than sham and nanocmpounds. In the vitreous, Day 1 had 1.79 mean particles (SEM=0.457), and Day 7 had mean 7.28 particles (SEM=1.910) vs no particle in sham group. On the retina, Day 1 had a mean length of 105.57µmµ (SEM=29.288), and Day 7 had a mean length of 326.04 (SEM=27.620) in RGD-nanocompound group. A 2-way ANOVA comparison of Pre-Injection vs. Day 1 and 1 month were conducted individually. Compared to Pre-Injection, the vitreous particles were significant on Day 1 and Day 7 (p<0.0001), but not present on day 14 and month one in RGD-nanocmpound, sham and nanocompounds. Compared to Pre-Injection, the length of particles on the retina were significant on Day 1 (p=0.0003) and persist until Day 21 (p<0.0001) but not present on nanocmpounds passed day 7.
Conclusions :
The findings of this study hold promise for the development of a targeted and effective therapeutic strategy for retinal ganglion cell. By leveraging the RGDs, specifically engineered for enhanced interaction with RGCs, this approach may pave the way for the treatment of retinal diseases, offering improved outcomes and preserving visual function in affected individuals.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.