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Abstract #76857 Published in IGR 19-3
Sustained Dorzolamide Release Prevents Axonal and Retinal Ganglion Cell Loss in a Rat Model of IOP-Glaucoma
Pitha I; Kimball EC; Oglesby EN; Pease ME; Fu J; Schaub J; Schaub J; Kim YC; Hu Q; Hanes J; Quigley HATranslational vision science & technology 2018; 7: 13
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; = 0.012, -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, = 0.03, -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]; = 0.02, -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.
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Classification:
11.16 Vehicles, delivery systems, pharmacokinetics, formulation (Part of: 11 Medical treatment)
5.1 Rodent (Part of: 5 Experimental glaucoma; animal models)
11.5.2 Topical (Part of: 11 Medical treatment > 11.5 Carbonic anhydrase inhibitors)
