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

Ian Pitha, Elizabeth C. Kimball, Ericka N. Oglesby, Mary Ellen Pease, Jie Fu, Julie Schaub, Yoo Chun Kim, Qi Hu, Justin S Hanes, Harry A Quigley

Research output: Contribution to journalArticle

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 X days in treated versus 227 ± 191 mm Hg X 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.

Original languageEnglish (US)
Article number13
JournalTranslational Vision Science and Technology
Volume7
Issue number2
DOIs
StatePublished - Mar 1 2018

Keywords

  • Carbonic anhydrase inhibitor
  • Controlled release
  • Poly(ether-anhydride)

ASJC Scopus subject areas

  • Ophthalmology
  • Biomedical Engineering

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