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: To determine the viability of using MRI measurement of optic nerve morphology as an objective analysis of glaucomatous damage. Retrospective study conducted at Tohoku University Hospital. Thirty-eight eyes of 19 patients with open angle glaucoma. Patients were scanned with T2-weighted and 3-T diffusion tensor MRI, and parameters of the optic nerve, including fractional anisotropy, apparent diffusion coefficient, and cross-sectional area, were determined. Conventional parameters of glaucomatous damage, including circumpapillary and macular retinal nerve fiber layer thickness, and mean deviation and average total deviation of the central 16 test points from the Humphrey Field Analyzer, were then compared to the MRI-derived parameters. Spearman's coefficient of correlation was calculated to determine the significance of the correlation. Correlation coefficient between the MRI parameters and the parameters of glaucomatous damage. Mean deviation was significantly correlated with all MRI parameters (fractional anisotropy: r = 0.53, apparent diffusion coefficient: r = -0.44, cross-sectional area: r = 0.70). Circumpapillary retinal nerve fiber layer thickness was significantly correlated with fractional anisotropy (r = 0.60) and cross-sectional area (r = 0.47), but not apparent diffusion coefficient (r = -0.29). Central macular function and macular retinal nerve fiber layer thickness were also significantly correlated with MRI parameters. Optic nerve MRI parameters were significantly correlated to glaucomatous damage. MRI analysis of the optic nerve may thus have value as an objective instrument to assess glaucomatous degeneration, including the function of the macula.Clinical and Experimental Ophthalmology 09/2013; · 1.96 Impact Factor
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ABSTRACT: The retinal ischemia-reperfusion injury (RIR) is a common pathological process that leads to progressive visual loss and blindness in many retinal diseases such as retinal vascular occlusion disease, diabetic retinopathy, and acute glaucoma. Currently, there has been no effective therapy. The purpose of this study was to investigate the effects of transplantation of retinal progenitor cells (RPCs) into the subretinal space (SRS) and the superior colliculus (SC) in a rat model of RIR injury. We used cultured postnatal day1 rat RPCs transfected with adeno-associated virus containing the cDNA encoding enhanced green fluorescence protein (EGFP) for transplantation. RIR injury was induced by increases in the intraocular pressure to 110mmHg for 60min. The effects of transplantation were evaluated by immunohistochemistry, electroretinography (ERG), and visual evoked potentials (VEP). We found that in rats with RIR injury, RPCs transplanted into the SRS and the SC survived for at least 8 weeks, migrated into surrounding tissues, and improved the ERG and VEP responses. Cells transplanted into the SC improved the VEP response more than those transplanted into the SRS. Our data suggest that transplantation of RPCs into the SRS and the SC may be a possible method for cell replacement therapy for retinal diseases.Neuroscience Letters 09/2013; · 2.03 Impact Factor
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ABSTRACT: Previous studies demonstrated that primary open angle glaucoma (POAG) is associated with abnormal brain structure; however, little is known about the changes in the local synchronization of spontaneous activity. The main objective of this study was to investigate spontaneous brain activity in patients with POAG using regional homogeneity (ReHo) analysis based on resting state functional magnetic resonance imaging (rs-fMRI). Thirty-nine POAG patients and forty-one age- and gender- matched healthy controls were finally included in the study. ReHo values were used to evaluate spontaneous brain activity and whole brain voxel-wise analysis of ReHo was carried out to detect differences by region in spontaneous brain activity between groups. Compared to controls, POAG patients showed increased ReHo in the right dorsal anterior cingulated cortex, the bilateral medial frontal gyrus and the right cerebellar anterior lobe, and decreased ReHo in the bilateral calcarine, bilateral precuneus gryus, bilateral pre/postcentral gyrus, left inferior parietal lobule and left cerebellum posterior lobe. A multiple linear regression analysis was performed to explore the relationships between clinical measures and ReHo by region showed significant group differences in the POAG group. Negative correlations were found between age and the ReHo values of the superior frontal gyrus (r = -0.323, p = 0.045), left calcarine (r = -0.357, p = 0.026) and inferior parietal lobule (r = -0.362, p = 0.024). A negative correlation was found between the ReHo values of the left precuneus and the cumulative mean defect (r = -0.400, p = 0.012). POAG was associated with abnormal brain spontaneous activity in some brain regions and such changed regional activity may be associated with clinical parameters. Spontaneous brain activity may play a role in POAG initiation and progression.PLoS ONE 01/2014; 9(2):e89493. · 3.73 Impact Factor