Sustained Dorzolamide Release Prevents Axonal and Retinal Ganglion Cell Loss in a Rat Model of IOP-Glaucoma.

Abstract

PURPOSE:

To determine if one injection of a sustained release formulation of dorzolamide in biodegradable microparticles (DPP) reduces retinal ganglion cell (RGC) loss in a rat model of glaucoma.

METHODS:

We injected either DPP or control microparticles intravitreally in 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 in treated 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 with control microparticle injection alone (RGC axon count reduction: 21% vs. 52%; RGC body reduction: 25% vs. 50% [beta tubulin labeling]; P = 0.02, t-test).

CONCLUSIONS:

A single injection of sustained release DPP protected against RGC loss and axial elongation in a rat model of IOP glaucoma.

TRANSLATIONAL RELEVANCE:

Sustained release IOP-lowering medications have the potential to stop glaucoma progression.

• Authors: Ian Pitha, Elizabeth C Kimball, Ericka N Oglesby, Mary Ellen Pease, Jie Fu, Julie Schaub, Yoo-Chun Kim, Qi Hu, Justin Hanes, Harry A Quigley
• Journal: Translational vision science & technology (Transl Vis Sci Technol) Vol. 7 Issue 2 Pg. 13 (Apr 2018) ISSN: 2164-2591 [Print] United States
• PMID: 29616152 (Publication Type: Journal Article)