Functional and Structural Analysis of the Visual System in the Rhesus Monkey Model of Optic Nerve Head Ischemia

A redistribution of neurochemicals has been identified in the visual cortex of monkeys with laser-induced glaucoma. Examined were functional, structural, and neurochemical changes to the retina, optic nerve, and central visual system in a nonhuman primate model of optic nerve head (ONH) ischemia cau...

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Bibliographic Details
Published in:	Investigative ophthalmology & visual science Vol. 45; no. 6; pp. 1830 - 1840
Main Authors:	Brooks, Dennis E, Kallberg, Maria E, Cannon, Richard L, Komaromy, Andras M, Ollivier, Franck J, Malakhova, Olga E, Dawson, William W, Sherwood, Mark B, Kuekuerichkina, Elen E, Lambrou, George N
Format:	Journal Article
Language:	English
Published:	Rockville, MD ARVO 01-06-2004 Association for Research in Vision and Ophtalmology
Subjects:	Animals Axons - pathology Biological and medical sciences Blood Flow Velocity Calbindins Cell Count Disease Models, Animal Diseases of visual field, optic nerve, optic chiasma and optic tracts Electrophysiology Endothelin-1 - toxicity Geniculate Bodies - metabolism Glaucoma and intraocular pressure Immunohistochemistry Infusion Pumps, Implantable Laser-Doppler Flowmetry Macaca mulatta Medical sciences Ophthalmology Optic Disk - blood supply Optic Nerve - metabolism Optic Nerve - physiopathology Optic Neuropathy, Ischemic - chemically induced Optic Neuropathy, Ischemic - metabolism Optic Neuropathy, Ischemic - physiopathology Proto-Oncogene Proteins c-fos - metabolism Retina - metabolism Retina - physiopathology Retinal Ganglion Cells - pathology S100 Calcium Binding Protein G - metabolism Tonometry, Ocular Visual Cortex - metabolism Visual Cortex - physiopathology Nervous system diseases Head Optic nerve Monkey Cardiovascular disease Functional analysis Vascular disease Visual system Eye disease Vertebrata Mammalia Cranial nerve disease Visual pathway Ischemia Animal Primates Models Ophthalmology Optic nerve ischemia Structural analysis
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Summary:	A redistribution of neurochemicals has been identified in the visual cortex of monkeys with laser-induced glaucoma. Examined were functional, structural, and neurochemical changes to the retina, optic nerve, and central visual system in a nonhuman primate model of optic nerve head (ONH) ischemia caused by sustained unilateral administration of endothelin (ET)-1 to the optic nerve. ET-1 or sham control solution was delivered by osmotic minipump to the retrolaminar region of one optic nerve of rhesus monkeys (Macaca mulatta) for 1.5 years. ONH topography and blood flow velocity were serially studied with scanning laser tomography and laser Doppler flowmetry, respectively. Retinal and cortical electrophysiologic measurements from pattern-derived stimuli were obtained quarterly. Immunohistochemistry was used to identify the distribution of calbindin (CB) and c-Fos labeled neurons in the visual cortex areas V1 and V2, and lateral geniculate nucleus (LGN). Retinal ganglion cell counts and optic nerve axon density were determined by light microscopy. No significant changes in retinal and ONH morphology, ONH blood flow velocity, and retinal and cortical pattern-derived functional activity were detected. Measurement of CB-positive cell density in V1 and V2 showed a significant decrease in CB labeling to the contralateral side of the ET-1-treated eye (P < 0.04). CB-positive cells were present in the magnocellular layers of the LGN with no differences noticed between the ET-1- and sham-treated eyes. c-Fos-labeled neurons were found in striate area V1 and extrastriateV2 of both groups. No c-Fos labeling was observed in the LGN. Administering ET-1 to the orbital optic nerve alters neuronal metabolic activity in the visual cortex in rhesus monkeys. Metabolic activity reductions in the visual cortex precede the ability to detect functional and structural alterations in the retina, ONH, and visual cortex in this animal model.
ISSN:	0146-0404 1552-5783 1552-5783
DOI:	10.1167/iovs.03-0950