dc.contributor.author | Lambert, Wendi S. | |
dc.contributor.author | Carlson, Brian J. | |
dc.contributor.author | Ghose, Purnima | |
dc.contributor.author | Vest, Victoria D. | |
dc.contributor.author | Yao, Vincent | |
dc.contributor.author | Calkins, David J. | |
dc.date.accessioned | 2020-07-16T16:30:58Z | |
dc.date.available | 2020-07-16T16:30:58Z | |
dc.date.issued | 2019-08-09 | |
dc.identifier.citation | sCIENTIFIC Reports | en_US |
dc.identifier.issn | 2045-2322 | |
dc.identifier.uri | http://hdl.handle.net/1803/10206 | |
dc.description.abstract | Glaucoma is a group of optic neuropathies associated with aging and sensitivity to intraocular pressure (IOP). The disease causes vision loss through the degeneration of retinal ganglion cell neurons and their axons in the optic nerve. Using an inducible model of glaucoma, we elevated IOP in the squirrel monkey (Saimiri boliviensis) using intracameral injection of 35 mu m polystyrene microbeads and measured common pathogenic outcomes in the optic projection. A 42% elevation in IOP over 28 weeks reduced anterograde transport of fluorescently-labeled cholera toxin beta from retina to the lateral geniculate nucleus (60% decrease), and to the superior colliculus (49% decrease). Pressure also reduced survival of ganglion cellaxons in the optic nerve by 22%. The same elevation caused upregulation of proteins associated with glaucomatous neurodegeneration in the retina and optic nerve, including complement 1q, interleukin 6, and brain-derived neurotrophic factor. That axon degeneration in the nerve lagged deficits in anterograde transport is consistent with progression in rodent models, while the observed protein changes also occur in tissue from human glaucoma patients. Thus, microbead occlusion in a non-human primate with a visual system similar to our own represents an attractive model to investigate neurodegenerative mechanisms and therapeutic interventions for glaucoma. | en_US |
dc.description.sponsorship | We thank the Steve and Michelle Kirsch Foundation, Glaucoma Research Foundation, Research to Prevent Blindness, Inc., EY017427, EY024997 and EY029903 for their support. The Vanderbilt Vision Research Center (Core Grant: P30 EY08126) provided use of the Vanderbilt University Apparatus Shop and Vanderbilt Department of Animal Care. Confocal imaging was performed in part through the use of the Vanderbilt Cell Imaging Shared Resource (supported by NIH grants UL1 RR024975, CA68485, DK20593, DK58404, DK59637 and EY08126). | en_US |
dc.language.iso | en_US | en_US |
dc.source.uri | https://www.nature.com/articles/s41598-019-48054-y#rightslink | |
dc.subject | OPTIC-NERVE HEAD | en_US |
dc.subject | INTRAOCULAR-PRESSURE | en_US |
dc.subject | AXONAL-TRANSPORT | en_US |
dc.subject | OCULAR HYPERTENSION | en_US |
dc.subject | NEW-WORLD | en_US |
dc.subject | AXONOPATHY | en_US |
dc.subject | RETINA | en_US |
dc.subject | MONKEY | en_US |
dc.subject | NEUROINFLAMMATION | en_US |
dc.subject | NEURODEGENERATION | en_US |
dc.title | Towards A Microbead Occlusion Model of Glaucoma for a Non-Human Primate | en_US |
dc.type | Article | en_US |
dc.identifier.doi | 10.1038/s41598-019-48054-y | |