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(Investigative Ophthalmology and Visual Science. 2004;45:1830-1840.)
© 2004 by The Association for Research in Vision and Ophthalmology, Inc.
DOI:  10.1167/iovs.03-0950
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Functional and Structural Analysis of the Visual System in the Rhesus Monkey Model of Optic Nerve Head Ischemia

Dennis E. Brooks,1 Maria E. Källberg,1 Richard L. Cannon,2 Andras M. Komàromy,1 Franck J. Ollivier,1 Olga E. Malakhova,2 William W. Dawson,3 Mark B. Sherwood,3 Elen E. Kuekuerichkina,2 and George N. Lambrou4

1From the Department of Small Animal Clinical Sciences, College of Veterinary Medicine, and the Departments of 2Neuroscience and 3Ophthalmology, College of Medicine, University of Florida, Gainesville, Florida; and 4Novartis Cibavision, Basel, Switzerland.

PURPOSE. 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.

METHOD. 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.

RESULTS. 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.

CONCLUSIONS. 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.






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