Functional and structural analysis of the visual system in the rhesus monkey model of optic nerve head ischemia.
OBJECTIVE
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.


METHODS
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.
Brooks
Dennis E
DE
Department of Small Animal Clinical Sciences, College of Veterinary Medicine, University of Florida, Gainesville 32608, USA. brooksd@mail.vetmed.ufl.edu
Källberg
Maria E
ME
Cannon
Richard L
RL
Komàromy
Andras M
AM
Ollivier
Franck J
FJ
Malakhova
Olga E
OE
Dawson
William W
WW
Sherwood
Mark B
MB
Kuekuerichkina
Elen E
EE
Lambrou
George N
GN
D000818:Animals; D001369:Axons / Q000473:pathology; D001783:Blood Flow Velocity; D064026:Calbindins; D002452:Cell Count; D004195:Disease Models, Animal; D004594:Electrophysiology; D019332:Endothelin-1 / Q000633:toxicity; D005829:Geniculate Bodies / Q000378:metabolism; D007150:Immunohistochemistry; D015918:Infusion Pumps, Implantable; D017078:Laser-Doppler Flowmetry; D008253:Macaca mulatta; D009898:Optic Disk / Q000098:blood supply*; D009900:Optic Nerve / Q000378:metabolism / Q000503:physiopathology*; D018917:Optic Neuropathy, Ischemic / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D012160:Retina / Q000378:metabolism / Q000503:physiopathology*; D012165:Retinal Ganglion Cells / Q000473:pathology; D064030:S100 Calcium Binding Protein G / Q000378:metabolism; D014065:Tonometry, Ocular; D014793:Visual Cortex / Q000378:metabolism / Q000503:physiopathology*
D064026:Calbindins; D019332:Endothelin-1; D016760:Proto-Oncogene Proteins c-fos; D064030:S100 Calcium Binding Protein G