Abstract
Purpose :
Retinal neovascularization causes many blinding retinal disorders, including diabetic retinopathy and exudative macular degeneration. While targeted therapy against VEGF is the primary treatment, some cases are not responsive to currently approved therapies. Previous studies have shown gold nanoparticles (GNP) to have an anti-angiogenic effect on retinal neovascularization. However, the toxic effect of GNP on retinal function is not well studied. Polyvinylidene fluoride (PVDF) is an FDA-approved polymer to be used inside the eye and is currently used in haptic intraocular lenses. Therefore, we hypothesized that coating GNP with PVDF may reduce the possible toxic effect while preserving the anti-angiogenic effect of gold nanoparticles.
Methods :
Monodisperse GNPs of 20nm were manufactured and replaced their citrate coating with PVP and PVDF layers. Polymer-coated GNPs were attached to functionalized barium titanate nanoparticle core cargo and confirmed with SEM. The proliferation assay of Human Retinal Epithelial Cells (HREC) were assessed in the presence of a different concentration of GNPs and polymer-coated GNP. The concentrations of 0.1, 1, 10, and 100 µg/mL GNP were tested. TUNEL assay determined cell apoptosis compared to a positive control containing DNase. Alamar Blue dye determined cell growth and normalized to show the samples' proliferation. Wild-type C57BL/6J mice aged 4–8 weeks were anesthetized and underwent IVI of GNPs vs. polymer-coated nanoparticles. ERG and OCT results were compared to pretreatment in the same animal for 14 days post-IVI.
Results :
Fluorescence intensity through TUNEL and proliferation assay analysis was normalized to show differentiation in apoptosis and proliferation between samples. Fluorescence was absent compared to the positive control, indicating no DNA breakdown due to GNP. It was observed that GNP concentrations above 10 µg/mL resulted in a lower intensity and consequently decreased cell proliferation in HRECs. We observed inhibited cell growth when incubated with 10 to 100 µg/mL GNP in Ames' media, while the same growth inhibition was observed with 100 µg/ml in the polymer-coated GNP. ERG and OCT images showed no difference in either GNPs or polymer-coated GNP.
Conclusions :
These findings may provide new evidence for using gold nanoparticles to manage retinal neovascularization and other future retinal applications.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.