Investigating the Effect of a Micelle-Based Drug Delivery System in Reducing IOP and Glaucomatous Effects in a Partially Open Angle Mouse Model of Glaucoma

Abstract

This project explores the use of a novel sustained release mucoadhesive micelle-based drug delivery system in combination with 0.005% latanoprost (LTP) on our partially open angle mouse model of glaucoma (AP-2β TMR-KO). We previously tested for LTP treatment in our model and found a reduction in intraocular pressure (IOP) 20 minutes following treatment. This information led us to investigate the long-term effect of LTP treatment and micelle loaded with LTP (MLTP) treatment in our model. We hypothesized that the MLTP treatment would be more effective in reducing IOP and preventing glaucomatous effects than LTP treatment alone in the AP-2β TMR-KO mice. The MLTP groups of animals (wildtype and mutant) were treated every 3 days, and this was compared with animals treated with LTP daily as well as animals treated every 3 days with LTP alone for comparison’s sake for 60 days. IOP measurements were taken every 3 days. Following long term LTP treatment alone, mutant mice showed a consistent decrease in their baseline IOPs with a significant reduction in baseline IOP at 35 days of treatment across all cohorts (P<0.0001). In comparison, mutants treated with MLTP exhibited an even greater reduction in baseline IOP following long term treatment. After the treatment period, mice were euthanized, and their eyes were enucleated, fixed, sectioned, and stained for retinal ganglion cells (RGCs) using Brn3a. Mutant mice exhibited a significant decrease in RGC cell number when compared to wildtype, and this loss was not rescued by treatment with LTP. However, mutants treated with MLTP demonstrated significant RGC cell protection compared to eyes of untreated mutants, as well as everyday LTP treated mutants.