Morphological changes in the visual pathway induced by experimental glaucoma in Japanese monkeys.
ABSTRACT Glaucoma, an optic neuropathy, is the leading cause of world blindness. In this condition, the damage extends from the retina to the visual center in the brain, although the primary region of damage is thought to be the optic nerve head (ONH), with the lateral geniculate nucleus (LGN) being secondarily affected. We investigated time-dependent alterations in the ONH, the optic nerve (ON), and the LGN after intraocular pressure (IOP) elevation in Japanese monkeys (a species more similar to humans than other macaque species). Nine Japanese monkeys, each with an experimental glaucomatous left eye, and two naive monkeys were studied. Ocular-testing sessions (including IOP measurement and fundus photography) were held weekly. Eyes and brains were enucleated at 2-48 weeks after IOP elevation, and alterations in ONs and LGN were evaluated. The IOP of the treated eyes was monitored periodically and found to be elevated continuously throughout the observation period in each monkey. The ONH of the glaucomatous eyes exhibited time-dependent deep cupping and thinning of the rim area from 2 weeks after the IOP elevation. Loss of axons and a decrease in the area of ON were first observed at 4 and 28 weeks, respectively. Neuronal loss was first observed at 2 weeks in layers 1 and 2 of LGN [magnocellular (M)-layer] and at 12 weeks in layers 3-6 of LGN [parvocellular (P)-layer]. Neuronal shrinkage was first observed at 2 weeks in all layers in LGN. These findings indicate that in Japanese monkeys, damage to neurons in LGN can be detected in the early phase (first few weeks) after an IOP elevation, as can damage to ONH.
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ABSTRACT: Glaucoma is a leading cause of world blindness, and retinal ganglion cell death is its pathological hallmark. There is accumulating evidence that glaucomatous damage extends from retinal ganglion cells to vision centers in the brain. In an experimental primate model of unilateral glaucoma, degenerative changes are observed in magnocellular, parvocellular, and koniocellular pathways in the lateral geniculate nucleus, and these changes are presented in relation to intraocular pressure and the severity of optic nerve damage. Neuropathological findings are also present in lateral geniculate nucleus layers driven by the unaffected fellow eye. Finally, there is information on changes in the visual cortex in relation to varying degrees of retinal ganglion cell loss. The implications of these findings for refining concepts regarding the pathobiology of progression, and the detection and treatment of glaucoma, are discussed.Progress in Retinal and Eye Research 08/2003; 22(4):465-81. · 9.44 Impact Factor
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ABSTRACT: To determine whether parasol retinal ganglion cells (magnocellular pathway) are selectively lost in the primate model of glaucoma. Ocular hypertension was induced in one eye of six Macaca fascicularis monkeys for 6-14 weeks. The retinal ganglion cells in these eyes were labelled retrogradely with the tracer horseradish peroxidase (HRP) implanted into the optic nerve and subsequently examined in retinal whole mount preparations. The degree of retinal ganglion cell loss was estimated from Nissl stained tissue by comparison with the contralateral untreated control eye. In the three glaucomatous retinas with the best labelling 1282 cells could be classified, of which 182 were parasol cells and 1100 were midget cells. Linear regression analysis did not demonstrate a significant reduction in the proportion of parasol to midget cells with increasing cell loss (regression slope 0.023, 95% CI -0.7 to 0.11). Compared with the control eye the cell soma of the remaining retinal ganglion cells in glaucomatous eyes were reduced in size by 20% for parasol cells (p=0.003) and by 16% for midget cells (p <0.001). The results of this study do not support the hypothesis that selective loss of parasol retinal ganglion cells occurs in experimental glaucoma. In addition, the change in cell soma size distributions following ocular hypertension suggests that both parasol and midget retinal ganglion cells undergo shrinkage before cell death.British Journal of Ophthalmology 03/2000; 84(3):303-10. · 2.73 Impact Factor
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ABSTRACT: To examine the expression and localization of heat shock proteins (HSPs) in the retinas of normal and experimentally induced primate glaucoma eyes. These proteins are known to be produced in response to a variety of stresses. Experimental glaucoma was induced in the right eyes of three adult monkeys by repeated applications of argon laser to the chamber angle. Immunostaining with a panel of antibodies against HSP 90, 70, 60, 47, and 27 was performed on retinal sections prepared from the normal and glaucomatous monkey eyes. The intensity of immunostaining for HSP 90, 60, and 27 was greatly enhanced in the retinas of glaucomatous eyes. Prominent reactivity was observed in the inner retinal layers, especially in the ganglion cell and nerve fiber layers. The staining intensity for HSP 70 was also moderately increased, while immunoreactivity against HSP 47 remained almost unchanged in glaucomatous retinas. Immunostaining against glial fibrillary acidic protein was increased and the immunolabeling pattern appeared to be identical with that of HSP 90 in glaucoma retinas. The level of HSP 90, 70, 60, and 27 in primate retinas was increased in experimentally induced ocular hypertension. The differences in expression pattern suggest that each HSP may have its unique role in responding to damage or injury related to intraocular pressure elevation.Japanese Journal of Ophthalmology 01/2003; 47(1):42-52. · 1.27 Impact Factor