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PloS One 2016Visual function has been shown to deteriorate prior to the onset of retinopathy in some diabetic patients and experimental animal models. This suggests the involvement...
Visual function has been shown to deteriorate prior to the onset of retinopathy in some diabetic patients and experimental animal models. This suggests the involvement of the brain's visual system in the early stages of diabetes. In this study, we tested this hypothesis by examining the integrity of the visual pathway in a diabetic rat model using in vivo multi-modal magnetic resonance imaging (MRI). Ten-week-old Sprague-Dawley rats were divided into an experimental diabetic group by intraperitoneal injection of 65 mg/kg streptozotocin in 0.01 M citric acid, and a sham control group by intraperitoneal injection of citric acid only. One month later, diffusion tensor MRI (DTI) was performed to examine the white matter integrity in the brain, followed by chromium-enhanced MRI of retinal integrity and manganese-enhanced MRI of anterograde manganese transport along the visual pathway. Prior to MRI experiments, the streptozotocin-induced diabetic rats showed significantly smaller weight gain and higher blood glucose level than the control rats. DTI revealed significantly lower fractional anisotropy and higher radial diffusivity in the prechiasmatic optic nerve of the diabetic rats compared to the control rats. No apparent difference was observed in the axial diffusivity of the optic nerve, the chromium enhancement in the retina, or the manganese enhancement in the lateral geniculate nucleus and superior colliculus between groups. Our results suggest that streptozotocin-induced diabetes leads to early injury in the optic nerve when no substantial change in retinal integrity or anterograde transport along the visual pathways was observed in MRI using contrast agent enhancement. DTI may be a useful tool for detecting and monitoring early pathophysiological changes in the visual system of experimental diabetes non-invasively.
Topics: Animals; Contrast Media; Diabetes Mellitus, Experimental; Diffusion Magnetic Resonance Imaging; Humans; Rats; Rats, Sprague-Dawley; Streptozocin; Visual Pathways
PubMed: 27768755
DOI: 10.1371/journal.pone.0165169 -
PloS One 2014Loss of retinal ganglion cells in in non-optic neuritis eyes of Multiple Sclerosis patients (MS-NON) has recently been demonstrated. However, the pathological basis of...
PURPOSE
Loss of retinal ganglion cells in in non-optic neuritis eyes of Multiple Sclerosis patients (MS-NON) has recently been demonstrated. However, the pathological basis of this loss at present is not clear. Therefore, the aim of the current study was to investigate associations of clinical (high and low contrast visual acuity) and electrophysiological (electroretinogram and multifocal Visual Evoked Potentials) measures of the visual pathway with neuronal and axonal loss of RGC in order to better understand the nature of this loss.
METHODS
Sixty-two patients with relapsing remitting multiple sclerosis with no previous history of optic neuritis in at least one eye were enrolled. All patients underwent a detailed ophthalmological examination in addition to low contrast visual acuity, Optical Coherence Tomography, full field electroretinogram (ERG) and multifocal visual evoked potentials (mfVEP).
RESULTS
There was significant reduction of ganglion cell layer thickness, and total and temporal retinal nerve fibre layer (RNFL) thickness (p<0.0001, 0.002 and 0.0002 respectively). Multifocal VEP also demonstrated significant amplitude reduction and latency delay (p<0.0001 for both). Ganglion cell layer thickness, total and temporal RNFL thickness inversely correlated with mfVEP latency (r = -0.48, p<0.0001 respectively; r = -0.53, p<0.0001 and r = -0.59, p<0.0001 respectively). Ganglion cell layer thickness, total and temporal RNFL thickness also inversely correlated with the photopic b-wave latency (r = -0.35, p = 0.01; r = -0.33, p = 0.025; r = -0.36, p = 0.008 respectively). Multivariate linear regression model demonstrated that while both factors were significantly associated with RGC axonal and neuronal loss, the estimated predictive power of the posterior visual pathway damage was considerably larger compare to retinal dysfunction.
CONCLUSION
The results of our study demonstrated significant association of RGC axonal and neuronal loss in NON-eyes of MS patients with both retinal dysfunction and post-chiasmal damage of the visual pathway.
Topics: Adult; Axons; Electroretinography; Evoked Potentials, Visual; Female; Humans; Male; Middle Aged; Multiple Sclerosis, Relapsing-Remitting; Retina; Tomography, Optical Coherence; Visual Acuity; Visual Pathways
PubMed: 25166273
DOI: 10.1371/journal.pone.0102546 -
Journal of Neurophysiology Oct 2017Visual object information is conveyed from V1 to area TE along the ventral visual pathway with increasing receptive field (RF) sizes. The RFs of TE neurons are known to...
Visual object information is conveyed from V1 to area TE along the ventral visual pathway with increasing receptive field (RF) sizes. The RFs of TE neurons are known to be large, but it is largely unknown how large RFs are shaped along the ventral visual pathway. In this study, we addressed this question in two aspects, static and dynamic mechanisms, by recording neural responses from macaque area TE and V4 to object stimuli presented at various locations in the visual field. As a component related to static mechanisms, we found that in area TE, but not in V4, response latency to objects presented at fovea were different from objects in periphery. As a component of the dynamic mechanisms, we examined effects of spatial attention on the RFs of TE neurons. Spatial attention did not affect response latency but modulated response magnitudes depending on attended location, shifting of the longitudinal axis of RFs toward the attended locations. In standard models of large RF formation, downstream neurons pool information from nearby RFs, and this process is repeated across the visual field and at each step along the ventral visual pathway. The present study revealed that this mechanism is not that simple: ) different circuit mechanisms for foveal and peripheral visual fields may be situated between V4 and area TE, and ) spatial attention dynamically changes the shape of RFs. Receptive fields (RFs) of neurons are progressively increased along the ventral visual pathway so that an RF at the final stage, area TE, covers a large area of the visual field. We explored the mechanism and suggested involvement of parallel circuit mechanisms between V4 and TE for foveal and peripheral parts of visual field. We also found a dynamic component of RF shape formation through attentional modulation of responses in a location-dependent manner.
Topics: Animals; Female; Fovea Centralis; Macaca; Male; Neurons; Reaction Time; Visual Cortex; Visual Fields; Visual Pathways
PubMed: 28768740
DOI: 10.1152/jn.00348.2017 -
Neuropsychologia Apr 2022The human cortical visual system consists of two major pathways, a ventral pathway which subserves perception and a dorsal pathway which primarily subserves visuomotor...
The human cortical visual system consists of two major pathways, a ventral pathway which subserves perception and a dorsal pathway which primarily subserves visuomotor control. Previous studies have found that children with cortical resections of the ventral visual pathway retain largely normal visuoperceptual abilities. Whether visually guided actions, supported by computations carried out by the dorsal pathway, follow a similar pattern of preservation remains unknown. To address this question, we examined visuoperceptual and visuomotor behaviors in a pediatric patient, TC, who underwent a cortical resection that included portions of the left ventral and dorsal pathways. We collected kinematic data when TC used her right and left hands to perceptually estimate the width of blocks that varied in width and length, and, separately, to grasp the same blocks. TC's perceptual estimation performance was comparable to that of controls, independent of the hand used. In contrast, relative to controls, she showed reduced visuomotor sensitivity to object shape and this was more evident when she grasped the objects with her contralesional right hand. These results provide novel evidence for a striking difference in the competence of the two visual pathways to cortical injuries acquired in childhood.
Topics: Child; Female; Hand; Hand Strength; Humans; Psychomotor Performance; Visual Pathways; Visual Perception
PubMed: 35182580
DOI: 10.1016/j.neuropsychologia.2022.108182 -
NeuroImage Oct 2022There is substantial variation between healthy individuals in the number of retinal ganglion cells (RGC) in the eye, with commensurate variation in the number of axons...
There is substantial variation between healthy individuals in the number of retinal ganglion cells (RGC) in the eye, with commensurate variation in the number of axons in the optic tracts. Fixel-based analysis of diffusion MR produces estimates of fiber density (FD) and cross section (FC). Using these fixel measurements along with retinal imaging, we asked if individual differences in RGC tissue volume are correlated with individual differences in FD and FC measurements obtained from the optic tracts, and subsequent structures along the cortical visual pathway. We find that RGC endowment is correlated with optic tract FC, but not with FD. RGC volume had a decreasing relationship with measurements from subsequent regions of the visual system (LGN volume, optic radiation FC/FD, and V1 surface area). However, we also found that the variations in each visual area were correlated with the variations in its immediately adjacent visual structure. We only observed these serial correlations when FC is used as the measure of interest for the optic tract and radiations, but no significant relationship was found when FD represented these white matter structures. From these results, we conclude that the variations in RGC endowment, LGN volume, and V1 surface area are better predicted by the overall cross section of the optic tract and optic radiations as compared to the intra-axonal restricted signal component of these white matter pathways. Additionally, the presence of significant correlations between adjacent, but not distant, anatomical structures suggests that there are multiple, local sources of anatomical variation along the visual pathway.
Topics: Financial Management; Humans; Nerve Fibers; Optic Tract; Retinal Ganglion Cells; Visual Pathways
PubMed: 35868617
DOI: 10.1016/j.neuroimage.2022.119495 -
Journal of Neuroinflammation Aug 2017Multiple sclerosis (MS) is an inflammatory demyelinating disease classically associated with axonal damage and loss; more recently, however, synaptic changes have been...
BACKGROUND
Multiple sclerosis (MS) is an inflammatory demyelinating disease classically associated with axonal damage and loss; more recently, however, synaptic changes have been recognized as additional contributing factors. An anatomical area commonly affected in MS is the visual pathway; yet, changes other than those associated with inflammatory demyelination of the optic nerve, i.e., optic neuritis, have not been described in detail.
METHODS
Adult mice were subjected to a diet containing cuprizone to mimic certain aspects of inflammatory demyelination as seen in MS. Demyelination and inflammation were assessed by real-time polymerase chain reaction and immunohistochemistry. Synaptic changes associated with inflammatory demyelination in the dorsal lateral geniculate nucleus (dLGN) were determined by immunohistochemistry, Western blot analysis, and electrophysiological field potential recordings.
RESULTS
In the cuprizone model, demyelination was observed in retinorecipient regions of the subcortical visual system, in particular the dLGN, where it was found accompanied by microglia activation and astrogliosis. In contrast, anterior parts of the pathway, i.e., the optic nerve and tract, appeared largely unaffected. Under the inflammatory demyelinating conditions, as seen in the dLGN of cuprizone-treated mice, there was an overall decrease in excitatory synaptic inputs from retinal ganglion cells. At the same time, the number of synaptic complexes arising from gamma-aminobutyric acid (GABA)-generating inhibitory neurons was found increased, as were the synapses that contain the N-methyl-D-aspartate receptor (NMDAR) subunit GluN2B and converge onto inhibitory neurons. These synaptic changes were functionally found associated with a shift toward an overall increase in network inhibition.
CONCLUSIONS
Using the cuprizone model of inflammatory demyelination, our data reveal a novel form of synaptic (mal)adaption in the CNS that is characterized by a shift of the excitation/inhibition balance toward inhibitory network activity associated with an increase in GABAergic inhibitory synapses and a possible increase in excitatory input onto inhibitory interneurons. In addition, our data recognize the cuprizone model as a suitable tool in which to assess the effects of inflammatory demyelination on subcortical retinorecipient regions of the visual system, such as the dLGN, in the absence of overt optic neuritis.
Topics: Animals; Chelating Agents; Corpus Callosum; Cuprizone; Demyelinating Diseases; Geniculate Bodies; Male; Mice; Mice, Inbred C57BL; Visual Pathways
PubMed: 28821276
DOI: 10.1186/s12974-017-0936-0 -
The Journal of Comparative Neurology May 2018Prior to forming and refining synaptic connections, axons of projection neurons navigate long distances to their targets. While much is known about guidance cues for...
Prior to forming and refining synaptic connections, axons of projection neurons navigate long distances to their targets. While much is known about guidance cues for axon navigation through intermediate choice points, whether and how axons are organized within tracts is less clear. Here we analyze the organization of retinal ganglion cell (RGC) axons in the developing mouse retinogeniculate pathway. RGC axons are organized by both eye-specificity and topography in the optic nerve and tract: ipsilateral RGC axons are segregated from contralateral axons and are offset laterally in the tract relative to contralateral axon topographic position. To identify potential cell-autonomous factors contributing to the segregation of ipsilateral and contralateral RGC axons in the visual pathway, we assessed their fasciculation behavior in a retinal explant assay. Ipsilateral RGC neurites self-fasciculate more than contralateral neurites in vitro and maintain this difference in the presence of extrinsic chiasm cues. To further probe the role of axon self-association in circuit formation in vivo, we examined RGC axon organization and fasciculation in an EphB1 mutant, in which a subset of ipsilateral RGC axons aberrantly crosses the midline but targets the ipsilateral zone in the dorsal lateral geniculate nucleus on the opposite side. Aberrantly crossing axons retain their association with ipsilateral axons in the contralateral tract, indicating that cohort-specific axon affinity is maintained independently of guidance signals present at the midline. Our results provide a comprehensive assessment of RGC axon organization in the retinogeniculate pathway and suggest that axon self-association contributes to pre-target axon organization.
Topics: Amino Acids; Animals; Animals, Newborn; Axons; Embryo, Mammalian; Eye; Fasciculation; Functional Laterality; In Vitro Techniques; Intermediate Filaments; Luminescent Proteins; Mice; Mice, Inbred C57BL; Mice, Transgenic; Optic Nerve; Receptor, EphB1; Retinal Ganglion Cells; Serotonin Plasma Membrane Transport Proteins; Visual Pathways
PubMed: 29322522
DOI: 10.1002/cne.24392 -
Current Opinion in Neurology Oct 2018Optical coherence tomography (OCT) is a noninvasive in-vivo imaging tool that enables the quantification of the various retinal layer thicknesses. Given the frequent... (Review)
Review
PURPOSE OF REVIEW
Optical coherence tomography (OCT) is a noninvasive in-vivo imaging tool that enables the quantification of the various retinal layer thicknesses. Given the frequent involvement of the visual pathway in multiple sclerosis, OCT has become an important tool in clinical practice, research and clinical trials. In this review, the role of OCT as a means to investigate visual pathway damage in multiple sclerosis is discussed.
RECENT FINDINGS
Evidence from recent OCT studies suggests that the peripapillary retinal nerve fibre layer (pRNFL) appears to be an ideal marker of axonal integrity, whereas the macular ganglion cell and inner plexiform layer (GCIP) thickness enables early detection of neuronal degeneration in multiple sclerosis. The thickness of the macular inner nuclear layer (INL) has been suggested as a biomarker for inflammatory disease activity and treatment response in multiple sclerosis. OCT parameters may also be used as an outcome measure in clinical trials evaluating the neuroprotective or regenerative potential of new treatments.
SUMMARY
OCT provides insights into multiple sclerosis beyond the visual pathway. It is capable of quantifying the major pathological hallmarks of the disease, specifically inflammation and neuroaxonal degeneration. OCT, therefore, has the potential to become another mainstay in the monitoring of multiple sclerosis patients.
Topics: Humans; Multiple Sclerosis; Tomography, Optical Coherence; Visual Pathways
PubMed: 30074495
DOI: 10.1097/WCO.0000000000000604 -
The European Journal of Neuroscience Apr 2019In albinism of all species, perturbed melanin biosynthesis in the eye leads to foveal hypoplasia, retinal ganglion cell misrouting, and, consequently, altered binocular... (Review)
Review
In albinism of all species, perturbed melanin biosynthesis in the eye leads to foveal hypoplasia, retinal ganglion cell misrouting, and, consequently, altered binocular vision. Here, written before he died, Ray Guillery chronicles his discovery of the aberrant circuitry from eye to brain in the Siamese cat. Ray's characterization of visual pathway anomalies in this temperature sensitive mutation of tyrosinase and thus melanin synthesis in domestic cats opened the exploration of albinism and simultaneously, a genetic approach to the organization of neural circuitry. I follow this account with a remembrance of Ray's influence on my work. Beginning with my postdoc research with Ray on the cat visual pathway, through my own work on the mechanisms of retinal axon guidance in the developing mouse, Ray and I had a continuous and rich dialogue about the albino visual pathway. I will present the questions Ray posed and clues we have to date on the still-elusive link between eye pigment and the proper balance of ipsilateral and contralateral retinal ganglion cell projections to the brain.
Topics: Albinism, Ocular; Animals; Cats; Genetics; History, 20th Century; History, 21st Century; Mice; Monophenol Monooxygenase; Neurosciences; Retina; Visual Pathways
PubMed: 30801828
DOI: 10.1111/ejn.14396 -
Investigative Ophthalmology & Visual... Dec 2014Neonatal hypoxia-ischemia is a major cause of brain damage in infants and may frequently present visual impairments. Although advancements in perinatal care have...
PURPOSE
Neonatal hypoxia-ischemia is a major cause of brain damage in infants and may frequently present visual impairments. Although advancements in perinatal care have increased survival, the pathogenesis of hypoxic-ischemic injury and the long-term consequences to the visual system remain unclear. We hypothesized that neonatal hypoxia-ischemia can lead to chronic, MRI-detectable structural and physiological alterations in both the eye and the brain's visual pathways.
METHODS
Eight Sprague-Dawley rats underwent ligation of the left common carotid artery followed by hypoxia for 2 hours at postnatal day 7. One year later, T2-weighted MRI, gadolinium-enhanced MRI, chromium-enhanced MRI, manganese-enhanced MRI, and diffusion tensor MRI (DTI) of the visual system were evaluated and compared between opposite hemispheres using a 7-Tesla scanner.
RESULTS
Within the eyeball, systemic gadolinium administration revealed aqueous-vitreous or blood-ocular barrier leakage only in the ipsilesional left eye despite comparable aqueous humor dynamics in the anterior chamber of both eyes. Binocular intravitreal chromium injection showed compromised retinal integrity in the ipsilesional eye. Despite total loss of the ipsilesional visual cortex, both retinocollicular and retinogeniculate pathways projected from the contralesional eye toward ipsilesional visual cortex possessed stronger anterograde manganese transport and less disrupted structural integrity in DTI compared with the opposite hemispheres.
CONCLUSIONS
High-field, multimodal MRI demonstrated in vivo the long-term structural and physiological deficits in the eye and brain's visual pathways after unilateral neonatal hypoxic-ischemic injury. The remaining retinocollicular and retinogeniculate pathways appeared to be more vulnerable to anterograde degeneration from eye injury than retrograde, transsynaptic degeneration from visual cortex injury.
Topics: Animals; Animals, Newborn; Disease Models, Animal; Eye; Follow-Up Studies; Hypoxia; Ischemia; Magnetic Resonance Imaging; Multimodal Imaging; Rats; Rats, Sprague-Dawley; Time Factors; Visual Cortex; Visual Pathways
PubMed: 25491295
DOI: 10.1167/iovs.14-14287