Sustained dorzolamide release prevents axonal and retinal ganglion cell loss in a rat model of IOP-glaucoma

Abstract

Purpose : IOP-lowering eye drops are a mainstay of glaucoma treatment; however, they require patient adherence, can be difficult to administer, and can cause ocular surface toxicity. Previously, we developed a microparticle formulation of dorzolamide (DPP) that lowers IOP in normotensive rabbits for over 30 days. We hypothesize that IOP lowering provided by a single application of DPP would prevent retinal ganglion cell (RGC) loss in a rat model of glaucoma.

Methods : We injected either DPP or control microparticles intravitreally in Wistar rats. Two days later, unilateral ocular hypertension was induced by translimbal, diode laser treatment by a surgeon masked to treatment group. IOP and clinical exams were performed until sacrifice 6 weeks after laser treatment. RGC loss was measured by masked observers in both optic nerve cross-sections and RGC layer counts from retinal whole mounts.

Results : Cumulative IOP exposure was significantly reduced by DPP injection: 49 + 48 mm Hg days versus 227 ± 191 mm Hg days in control microparticle eyes (p=0.012, t test). While control-injected eyes increased in axial length by 2.4 ± 1.7%, DPP eyes did not significantly enlarge (0.3 ± 2.2%, difference from control, p = 0.03, t test). RGC loss was significantly less in DPP eyes compared to microparticle injection alone (axon count reduction: 21% versus 52%; RGC reduction: 25% versus 50% (beta tubulin labeling); p=0.02, t test).

Conclusions : A single injection of DPP microparticles, reduced IOP elevation and RGC loss in a rat model of glaucoma. The results demonstrate that a single injection of a controlled release IOP-lowering formulation can reduce glaucomatous RGC loss.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.