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Sci Rep. 2017 Oct 30;7(1):14329. doi: 10.1038/s41598-017-14720-2.

Biomechanical, ultrastructural, and electrophysiological characterization of the non-human primate experimental glaucoma model.

Author information

1
Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California - Davis, Davis, California, 95616, United States of America.
2
Ocular Services On Demand (OSOD), Madison, Wisconsin, 53719, United States of America.
3
The Ocular Surface Institute, Department of Basic Sciences, College of Optometry, University of Houston, Houston, Texas, 77204, United States of America.
4
Covance Laboratories, Inc., Madison, Wisconsin, 53704, United States of America.
5
Department of Ophthalmology and Visual Sciences, School of Medicine and Public Health, University of Wisconsin - Madison, Madison, Wisconsin, 53792, United States of America.
6
Department of Anatomy and Neurobiology, School of Medicine, Boston University, Boston, Massachusetts, 02118, United States of America.
7
Department of Ophthalmology, School of Medicine, Boston University, Boston, Massachusetts, 02118, United States of America.
8
Department of Surgical Sciences, School of Veterinary Medicine, University of Wisconsin - Madison, Madison, Wisconsin, 53706, United States of America.
9
Ocular Services On Demand (OSOD), Madison, Wisconsin, 53719, United States of America. tmnork@wisc.edu.
10
Department of Ophthalmology and Visual Sciences, School of Medicine and Public Health, University of Wisconsin - Madison, Madison, Wisconsin, 53792, United States of America. tmnork@wisc.edu.
11
Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California - Davis, Davis, California, 95616, United States of America. cjmurphy@ucdavis.edu.
12
Ocular Services On Demand (OSOD), Madison, Wisconsin, 53719, United States of America. cjmurphy@ucdavis.edu.
13
Department of Ophthalmology & Vision Science, School of Medicine, University of California - Davis, Sacramento, California, 95817, United States of America. cjmurphy@ucdavis.edu.

Abstract

Laser-induced experimental glaucoma (ExGl) in non-human primates (NHPs) is a common animal model for ocular drug development. While many features of human hypertensive glaucoma are replicated in this model, structural and functional changes in the unlasered portions of trabecular meshwork (TM) of laser-treated primate eyes are understudied. We studied NHPs with ExGl of several years duration. As expected, ExGl eyes exhibited selective reductions of the retinal nerve fiber layer that correlate with electrophysiologic measures documenting a link between morphologic and elctrophysiologic endpoints. Softening of unlasered TM in ExGl eyes compared to untreated controls was observed. The degree of TM softening was consistent, regardless of pre-mortem clinical findings including severity of IOP elevation, retinal nerve fiber layer thinning, or electrodiagnostic findings. Importantly, this softening is contrary to TM stiffening reported in glaucomatous human eyes. Furthermore, microscopic analysis of unlasered TM from eyes with ExGl demonstrated TM thinning with collapse of Schlemm's canal; and proteomic analysis confirmed downregulation of metabolic and structural proteins. These data demonstrate unexpected and compensatory changes involving the TM in the NHP model of ExGl. The data suggest that compensatory mechanisms exist in normal animals and respond to elevated IOP through softening of the meshwork to increase outflow.

PMID:
29085025
PMCID:
PMC5662689
DOI:
10.1038/s41598-017-14720-2
[Indexed for MEDLINE]
Free PMC Article

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