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Impaired visual function in glaucoma.

OBJECTIVE: This work aims to evaluate whether glaucomatous visual field defects could be related to an impaired retinal function, to a delayed neural conduction in postretinal visual pathways, or both. METHODS: Visual field by Humphrey perimeter (central 24-2 threshold test) and simultaneous recordings of visual evoked potential (VEP) and pattern electroretinogram (PERG) were assessed in 21 subjects with open angle glaucoma (POAG) and in 15 age-matched controls (C). RESULTS: VEP: in POAG eyes we found P100 latency significantly (P<0.01) delayed when compared with controls and correlated with mean deviation (index of global visual field damage, MD) of 24-2 Humphrey perimetry (P<0.001); the P100 amplitudes were significantly (P<0.01) lower in POAG eyes than in control eyes and correlated with MD (P<0.001). PERG: POAG eyes showed P50 latency significantly (P<0.01) delayed when compared with controls and correlated with MD (P=0.002); the P50 and N95 amplitudes were significantly (P<0.01) lower in POAG than in control eyes and correlated with MD (P50: P=0.006; N95: P=0.002). Retinocortical time (RCT: difference between VEP P100 and PERG P50 latencies) and latency window (LW: difference between VEP N75 and PERG P50 latencies) were significantly (P<0.01) longer in POAG eyes than in control eyes and correlated with MD (RCT: P<0.001; LW: P<0.001). No significant correlations (P>0.05) were found between electrophysiological parameters and the corrected pattern standard deviation (index of localized visual field damage) of 24-2 Humphrey perimetry. CONCLUSION: In patients with open angle glaucoma the reduction of the index of global visual field damage (MD) could be ascribed to two sources of functional impairment: one retinal (impaired PERG) and one postretinal (delayed RCT and LW). In the postretinal impairment, a postsynaptic degeneration at the level of the lateral geniculate nucleus could be suggested.

Electroretinography↗

Vector analysis of visual evoked potentials in migraineurs with visual aura.

OBJECTIVE: To assess the capability of vector analysis of visual evoked potentials (VEPs) for revealing alterations in posterior visual pathways in migraineurs with visual aura. METHODS: VEPs to pattern reversal (PR) and LED goggle stimulation were obtained in 23 patients suffering from migraine with visual aura, in an orthogonal Fpz-Oz and T3-T4 montage and displayed as a two-channel Lissajous' trajectory. VEP latency and amplitude at Fpz-Oz, bc segment amplitude (V) and bc vector orientation angle (theta) were compared with a previously collected normative database for individual assessment, and group comparisons with the previously collected normal sample were made. Electrophysiological measures were also correlated with time from onset of disease and from the last crisis, and with the side of symptoms. RESULTS: No individual alterations in VEP latency or amplitude were observed. However, 36.4% of patients showed alterations in vector orientation to PR and 78% to LED goggles. Group differences with respect to normal subjects were found not only in vector orientation but also in midline VEP and V, only for PR stimulation. A significant relationship was found between the laterality of vector deviation and the laterality of symptoms. CONCLUSIONS: Vector analysis of VEP revealed alterations possibly corresponding to asymmetrical visual cortex activation in migraineurs with visual aura, mainly to diffuse light stimulation. SIGNIFICANCE: An electrophysiological parameter of individual value for revealing asymmetric activation of visual cortex in migraineurs is proposed.

Adolescent↗

Retinal and optic nerve diseases.

A variety of disease processes can affect the retina and/or the optic nerve, including vascular or ischemic disease, inflammatory or infectious disease, and degenerative disease. These disease processes may selectively damage certain parts of the retina or optic nerve, and the specific areas that are damaged may have implications for the design of potential therapeutic visual prosthetic devices. Outer retinal diseases include age-related macular degeneration, pathologic myopia, and retinitis pigmentosa. Although the retinal photoreceptors may be lost, the inner retina is relatively well-preserved in these diseases and may be a target for retinal prosthetic devices. Inner retinal diseases include retinal vascular diseases such as diabetic retinopathy, retinal venous occlusive disease, and retinopathy of prematurity. Other retinal diseases such as ocular infections (retinitis, endophthalmitis) may affect all retinal layers. Because the inner retinal cells, including the retinal ganglion cells, may be destroyed in these diseases (inner retinal or whole retinal), prosthetic devices that stimulate the inner retina may not be effective. Common optic nerve diseases include glaucoma, optic neuritis, and ischemic optic neuropathy. Because the ganglion cell nerve fibers themselves are damaged, visual prosthetics for these diseases will need to target more distal portions of the visual pathway, such as the visual cortex. Clearly, a sound understanding of retinal and optic nerve disease pathophysiology is critical for designing and choosing the optimal visual prosthetic device.

Diabetic Retinopathy↗

[Visual disorders as key symptoms of ocular migraine].

Vascular disturbance of the anterior visual pathways characterized by monocular visual experiences are sometimes caused by migraine. Retinal or ophthalmic migraine, a variant of complicated migraine, is distinctly rare. Two cases of female patients with ophthalmic migraine are reported. The relationships between the use of oral contraceptives and pregnancy are discussed.

Adult↗

Visualizing reaction pathways in photoactive yellow protein from nanoseconds to seconds.

Determining 3D intermediate structures during the biological action of proteins in real time under ambient conditions is essential for understanding how proteins function. Here we use time-resolved Laue crystallography to extract short-lived intermediate structures and thereby unveil signal transduction in the blue light photoreceptor photoactive yellow protein (PYP) from Halorhodospira halophila. By analyzing a comprehensive set of Laue data during the PYP photocycle (forty-seven time points from one nanosecond to one second), we track all atoms in PYP during its photocycle and directly observe how absorption of a blue light photon by its p-coumaric acid chromophore triggers a reversible photocycle. We identify a complex chemical mechanism characterized by five distinct structural intermediates. Structural changes at the chromophore in the early, red-shifted intermediates are transduced to the exterior of the protein in the late, blue-shifted intermediates through an initial "volume-conserving" isomerization of the chromophore and the progressive disruption of hydrogen bonds between the chromophore and its surrounding binding pocket. These results yield a comprehensive view of the PYP photocycle when seen in the light of previous biophysical studies on the system.

Bacterial Proteins↗

Pathway illuminated: visualizing protein kinase C signaling.

Protein kinase C has been at the center of cell signaling since the discovery 25 years ago that it transduces signals that promote phospholipid hydrolysis. In recent years, the use of genetically encoded fluorescent reporters has enabled studies of the regulation of protein kinase C signaling in living cells. Advances in imaging techniques have unveiled unprecedented detail of the signal processing mechanics of protein kinase C, from the second messengers calcium and diacylglycerol that regulate protein kinase C activity, to the locations and kinetics of different protein kinase C isozymes, to the spatial and temporal dynamics of substrate phosphorylation by this key enzyme. This review discusses how fluorescence imaging studies have illuminated the fidelity with which protein kinase C transduces rapidly changing extracellular information into intracellular phosphorylation signals.

Animals↗

Characterization of organelles in the vacuolar-sorting pathway by visualization with GFP in tobacco BY-2 cells.

We have shown the localization and mobilization of modified green fluorescent proteins (GFPs) with various signals in different compartments in a vacuolar-sorting system of tobacco BY-2 cells. In contrast to the efficient secretion of GFP from the transformed cells expressing SP-GFP composed of a signal peptide and GFP, accumulation of GFP in the vacuoles was observed in the cells expressing SP-GFP fused with the C-terminal peptide of pumpkin 2S albumin. This indicated that this peptide is sufficient for vacuolar targeting. Interestingly, the fluorescence in the vacuoles disappeared sharply at 7 d after inoculation of the cells, but it appeared again after re-inoculation into a new culture medium. When SP-GFP was fused with the region, termed PV72C, including a transmembrane domain and a cytosolic tail of a vacuolar-sorting receptor PV72, GFP-PV72C was detected in the Golgi-complex-like small particles. Prolonged culture showed that GFP-PV72C that reached the prevacuolar compartments was cleaved off the PV72C region to produce GFP, that arrived at the vacuoles to be diffused. These findings suggested that the vacuolar-sorting receptor might be recycled between the Golgi complex and prevacuolar compartments.

Base Sequence↗

Human primary visual cortex and lateral geniculate nucleus activation during visual imagery.

The functional magnetic resonance (fMRI) technique can be robustly used to map functional activation of the visual pathway including the primary visual cortex (V1), the lateral geniculate nucleus (LGN), and other nuclei of humans during visual perception stimulation. One of the major controversies in visual neuroscience is whether lower-order visual areas involve the visual imagery process. This issue was examined using fMRI at high magnetic field. It was demonstrated for the first time that the LGN was activated during visual imagery process in the human brain together with V1 and other activation. There was a tight coupling of the activation between V1 and the LGN during visual imagery.

Adult↗

Photoperiodic effects on thermoregulation in a 'blind' subterranean mammal.

Thermoregulatory responses to changes in photoperiod were studied in the 'blind' mole rat Spalax ehrenbergi (Nehring). Acclimation of cold-sensitive individuals to short photoperiod (8L:16D) at an ambient temperature (Ta) of 22 degrees C increased their thermoregulatory capacity in cold conditions, when compared to individuals which were acclimated to a photoperiod of 12L:12D at the same Ta. Acclimation of cold-resistant individuals to Ta = 17 degrees C but with a photoperiod of 16L:8D caused a decrease in thermoregulatory capacity. Evaluation of the visual pathway through the visual-evoked potentials showed that the mole rat does not respond to flash stimuli and can thus be considered to be effectively blind.

Animals↗

From three-dimensional space vision to prehensile hand movements: the lateral intraparietal area links the area V3A and the anterior intraparietal area in macaques.

The posterior parietal cortex is included in the dorsal cortical visual pathway underlying the three-dimensional (3-D) visual recognition of space and objects. The neurons in the lateral intraparietal area (LIP) respond visually to the three-dimensional objects, whereas those in the anterior intraparietal area (AIP) respond to hand movements to grasp them. LIP receives visual inputs from V3A, whereas AIP projects to the premotor areas; however, it is not known whether the neurons in LIP project to AIP. We herein investigated the connectional substrates that underlie the transformation of three-dimensional vision to prehensile hand movements in the Japanese monkey (Macaca fuscata). After identifying the three-dimensional visually responsive region in the posterior part of LIP by the unit recordings, we injected a bidirectional tracer, wheat germ agglutinin conjugated to horseradish peroxidase, into one of the recording sites. We found that LIP receives neuronal projections from V3A and sends axons to AIP. To confirm our findings, we injected several orthograde tracers into V3A and retrograde tracers into AIP in the same hemispheres. We found that the V3A neurons projecting to LIP terminate in the vicinity of the LIP neurons projecting to AIP. The results suggest that the cortical connections of V3A-LIP-AIP in the lateral bank of the intraparietal sulcus play an important role in the visuomotor transformation for prehensile hand movements.

Animals↗

Local cerebral glucose metabolic response to audiovisual stimulation and deprivation: studies in human subjects with positron CT.

Positron computed tomography (CT) and 18-F fluorodeoxyglucose (FDG) were used to measure local cerebral glucose metabolism (LCMRGlc) in patients and normal subjects during auditory and visual stimulation and deprivation. Sixty-six studies were performed in 42 individuals. In normal subjects metabolic left-right symmetry was found in states of partial (eyes patched or ears plugged) sensory deprivation. Visual stimuli of increasing complexity produced symmetric increases in LCMRGlc of the primary and associative visual cortices. Patients with lesions of the visual pathway but sparing the visual cortex demonstrated abnormalities in visual cortical LCMRGlc that correlated with clinical symptoms. Auditory stimulation studies in normal subjects demonstrated metabolic evidence of hemispheric specialization. The side (left versus right) and site of maximal metabolic response correlated with the type (verbal versus nonverbal) and content (factual story, chords, tone sequences) of the stimulus as well as the strategy used by the subject to solve the listening task. There was no correlation between the site of metabolic response and side of stimulus presentation. The results of these studies demonstrate that positron CT provides new and previously unattainable information about local human brain physiology in normal and pathological states. The limitations, advantages and future prospects of using these methods to study human brain function are discussed.

Aged↗

The optic lobe of Drosophila melanogaster. II. Sorting of retinotopic pathways in the medulla.

We present a quantitative evaluation of Golgi-impregnated columnar neurons in the optic lobe of wild-type Drosophila melanogaster. This analysis reveals the overall connectivity pattern between the 10 neuropil layers of the medulla and demonstrates the existence of at least three major visual pathways. Pathway 1 connects medulla layer M10 to the lobula plate. Input layers of this pathway are M1 and M5. Pathway 2 connects M9 to shallow layers of the lobula, which in turn are tightly linked to the lobula plate. This pathway gets major input via M2. Pathways 1 and 2 receive input from retinula cells R1-6, either via the lamina monopolar cell L1 (terminating in M1 and M5) or via L2 and T1 (terminating in M2). Neurons of these pathways typically have small dendritic fields. We discuss evidence that pathways 1 and 2 may play a major role in motion detection. Pathway 3 connects M8 to deep layers of the lobula. In M8 information converges that is derived either from M3 (pathway 3a) or from M4 and M6 (pathway 3b), layers that get their major input from L3 and R8 or L4 and R7, respectively. Some neurons of pathway 3 have large dendritic fields. We suggest that they may be involved in the computation of form and colour. Possible analogies to the organization of pathways in the visual system of vertebrates are discussed.

Animals↗

Current and future strategies in radiotherapy of childhood low-grade glioma of the brain. Part I: Treatment modalities of radiation therapy.

BACKGROUND: Treatment of childhood low-grade gliomas is a challenging issue owing to their low incidence and the lack of consensus about "optimal" treatment approach. MATERIAL AND METHODS: Reports in the literature spanning 60 years of radiation therapy, including orthovoltage, megavoltage and recently modern high-precision treatments, were reviewed with respect to visual function, survival, prognostic factors, dose prescriptions, target volumes, and treatment techniques. Based on these experiences, future strategies in the management of childhood low-grade glioma are presented. RESULTS: Evaluation of published reports is difficult because of inconsistencies in data presentation, relatively short follow-up in some series and failure to present findings and results in a comparable way. Even with the shortcomings of the reports available in the literature, primarily concerning indications, age at treatment, dose response, timing and use of "optimal" treatment fields, radiation therapy continues to play an important role in the management of these tumors achieving long-term survival rates up to 80% or more. Particularly in gliomas of the visual pathway, high local tumor control and improved or stable visual function is achieved in approximately 90% of cases. Data on dose-response relationships recommend dose prescriptions between 45 and 54 Gy with standard fractionation. There is consensus now to employ radiation therapy in older children in case of progressive disease only, regardless of tumor location and histologic subtype. In younger children, the role of radiotherapy is unclear. Recent advances in treatment techniques, such as 3-D treatment planning and various "high-precision" treatments achieved promising initial outcome, however with limited patient numbers and short follow-ups. CONCLUSIONS: Radiation therapy is an effective treatment modality in children with low-grade glioma regarding tumor control and improvement and/or preservation of neurologic function or vision, respectively. More prospective studies are needed to address the impact of modern radiation therapy technologies (including intensity-modulated radiotherapy) on outcome especially in the very young and to define the role of radiation therapy as a part of a comprehensive treatment approach. The forthcoming prospective trial SIOP/GPOH LGG RT 2003 is addressing this issue.

Adolescent↗

Registration of light stimuli in the cortically blind hemifield and its effect on localization.

Patients who suffer from unilateral damage to the geniculostriate system were asked to make a voluntary blink response whenever they guessed that a light stimulus was presented in their perimetrically blind hemifield. After about 600 trials they were able to register the presence of a light stimulus appearing in the 'blind' part of their visual field without any conscious visual access and, additionally, without any link to correct verbal responses. The patients' ability to localize targets presented in the hemianopic part of the visual field was at a high level of accuracy (as judged by their saccadic responses) after this procedure. The results indicate that there is a common extrastriate visual pathway subserving the performance in registration and localization of visual stimuli.

Adult↗

Selective mechanisms for complex visual patterns revealed by adaptation.

A great deal is known about the initial steps of visual processing. We know that humans have neural mechanisms selectively tuned to simple patterns of particular spatial frequencies and orientations. We also know that much later in the visual pathway, in inferotemporal cortex, cells respond to extremely complex visual patterns such as images of faces. Very little is known about intermediate levels of visual processing, where early visual signals are presumably combined to represent increasingly complex visual features. Here we show the existence of visual mechanisms in humans, tuned and selective to particular combinations of simple sinusoidal patterns, using a novel method of compound adaptation.

Acclimatization↗

Goldmann perimetry in acromegaly: a survey of 307 cases from 1951 through 1996.

OBJECTIVE: Because visual pathway lesions are a common complication of pituitary tumors, visual field examinations in patients with acromegaly were studied. Proportion and outcome of visual field defects in patients with acromegaly were evaluated. DESIGN: Large, retrospective case series. PARTICIPANTS: We reviewed 307 cases of acromegaly seen from 1951 through 1996 at a single referral center. METHODS: Kinetic visual field testing had been performed with the Goldmann perimeter, and the frequency of visual field defects and their correlation with other clinical manifestations and characteristics of the adenoma were examined. MAIN OUTCOME MEASURES: Repeat visual field examinations. RESULTS: Of the 307 patients included in the analysis, a visual field defect that could be attributed to the pituitary adenoma was observed in 62 (20.2%) during follow-up. Visual field defects were bilateral in 38 (61.3%) of these cases. Patients with visual field abnormalities were significantly younger (P = 0.04), had larger tumors (P < 0.001), had more suprasellar extensions (P < 0.001), and had higher levels of growth hormone in their serum (P = 0.04) than patients free of visual field defects. At the end of the follow-up period, visual field examination remained abnormal in 32 (10.4%). Return to a normal visual field examination after treatment was more frequently observed in patients who were less than 40 years of age at the time of diagnosis (P = 0.004). Secondary empty sella syndrome was the main cause of visual field defects after treatment. Abnormal visual field, either at the time of diagnosis or during follow-up, decreased from 27% of patients between 1951 and 1975 to 15.4% of patients between 1976 and 1996, when modern neuroimaging techniques became available. CONCLUSIONS: Endocrinologic and neuroimaging follow-up of patients with acromegaly should be accompanied by ophthalmic assessment. Factors predictive of visual field defects have been identified.

Acromegaly↗

The maintained discharge of neurons in the cat lateral geniculate nucleus: spectral analysis and computational modeling.

The maintained discharge of neurons along the early visual pathway in mammals constitutes the "noise" from which the visual signal must be discriminated. The statistics of this background noise in cat retinal ganglion cells (RGCs) have been shown to conform to that of a gamma-distributed renewal process (Kuffler et al., 1957; Barlow & Levick, 1969), and power spectrum analysis reveals that this property allows for low noise levels at the temporal-frequency range (0-10 Hz) most important for visual performance (Troy & Robson, 1992). In this study, we compare the statistics of the maintained discharge of cat lateral geniculate neurons with those of its RGC input by simultaneous recordings of spikes and S-potentials in single relay cells of the cat lateral geniculate nucleus (LGN). We demonstrate that, during primarily tonic spiking activity, the LGN maintained discharge preserves the renewal process statistics of its RGC input and also generates relatively little noise at the temporal frequencies important for vision. However, during burst spiking activity, the renewal process model breaks down and increased noise is generated at 2-10 Hz. This suggests that optimization of the visual signal/noise ratio is not a prime consideration in the behavioral states associated with bursting activity in the LGN. The occurrence of burst spikes in LGN relay cells is dependent on the activity of T-type calcium channels in their plasma membranes (Jahnsen & Llinas, 1984a,b). We show that a computational model of LGN relay cells that incorporates T-channel kinetics (Mukherjee & Kaplan, 1995) can correctly simulate LGN maintained discharge statistics during both tonic and bursty firing conditions, and indicates an essential role for this ion channel in determining the dynamic noise properties of the LGN. We also use the computational model to predict how the burstiness of the LGN maintained discharge is affected by the statistics of its RGC input.

Action Potentials↗