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Brian C Samuels, Christopher A Girkin, Lisa Hethcox, J Crawford C Downs, Wenjie Zhan; A Pilot Study for the Initial Validation of a Tree Shrew Model of Glaucoma. Invest. Ophthalmol. Vis. Sci. 2016;57(12):3572.
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© ARVO (1962-2015); The Authors (2016-present)
Retinal ganglion cell injury in glaucoma occurs at the level of the lamina cribrosa. Thus, there is increasing interest in understanding the mechanobiology of the optic nerve head. To study this, researchers need animal models that closely resemble the relevant human anatomy and develop key pathologic features of the human disease. While primates and rodents are the most widely used animal models of glaucoma, each has significant limitations. Tree shrews (Tupaia belangeri) are a mammalian species closely related to primates and offer the benefit of being accessible to most researchers and they have a load-bearing connective tissue lamina resembling primates. The purpose of this pilot study was to begin validating the magnetic bead occlusion model of experimental glaucoma in tree shrews.
Experimental glaucoma was induced in adult tree shrews (n=9) using a modified version of the magnetic bead occlusion method (Samsel et al; 2011). Briefly, magnetic beads were thoroughly washed and 0.1ml injected into the anterior chamber. Beads were directed to the angle using a magnet. All animals were followed for 3 months. Weekly IOP measurements were obtained using the iCare TonoLab tonometer and biweekly spectral domain optical coherence tomography (SDOCT) images of the optic nerve head were obtained using the Heidelberg Spectralis SD-OCT. At the end of the study, the eyes, optic nerves, and brains were fixed. Axon counts were completed and three-dimensional reconstructions of the optic nerve head were created for histomorphometric analysis.
IOP in the experimental glaucoma eye was significantly elevated compared to the fellow control eye each week (average weekly IOP = 23±3 vs 9±2 mmHg; p<0.001). Retinal nerve fiber layer (RNFL) thickness declined at a rate of 5.9um/week in the experimental glaucoma eyes and was unchanged in the control eye (Week 12 RNFL thickness = 76±35 vs 135±21 um; p<0.001). In vivo SD-OCT imaging showed cupping and posterior displacement of the lamina cribrosa in the glaucomatous eyes, which was confirmed by 3-D histomorphometry. Axon counts were reduced consistent with IOP elevation.
Additional model validation is required, but this pilot study confirms our belief that the tree shrews with experimental glaucoma develop key pathologic features of the human disease and this model has the potential to help researchers accelerate our understanding of glaucoma pathophysiology.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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