Retinal mechanisms determine the subadditive response to polychromatic light by the human circadian system

Light is the major synchronizer of circadian rhythms to the 24-h solar day. The intrinsically photosensitive retinal ganglion cells (ipRGCs) play a central role in circadian regulation but cones also provide, albeit indirectly, input to these cells. In humans, spectrally opponent blue versus yellow (b-y) bipolar cells lying distal to the ganglion cell layer were hypothesized to provide direct input to the ipRGCs and therefore, the circadian system should exhibit subadditivity to some types of polychromatic light. Ten subjects participated in a within-subjects 3-night protocol. Three experimental conditions were employed that provided the same total irradiance at both eyes: (1) one unit of blue light (lambda(max)=450 nm, 0.077 W/m(2)) to the left eye plus one unit of green light (lambda(max)=525 nm, 0.211 W/m(2)) to the right eye, (2) one unit of blue light to the right eye plus one unit of green light to the left eye, and (3) 1/2 unit of blue light plus 1/2 unit of green light to both eyes. The first two conditions did not differ significantly in melatonin suppression while the third condition had significantly less melatonin suppression than conditions 1 and 2. Furthermore, the magnitudes of suppression were well predicted by a previously published model of circadian phototransduction incorporating spectral opponency. As was previously demonstrated, these results show that the human circadian system exhibits a subadditive response to certain polychromatic light spectra. This study demonstrates for the first time that subadditivity is due to spectrally opponent (color) retinal neurons.     

Light exposure of chick embryo influences lateralized recall of imprinting memory

Environmental cues, such as light during the later part of incubation, are known to establish lateralization of some forms of visually guided behaviors in birds. The authors investigated the effect of light on lateralized recall of imprinting memory in chicks. On Day E19 of incubation, one eye was occluded for 24 hr. The other eye received stimulation by light. Chicks were imprinted and then tested for their imprinting preferences after administration of a low dose (500 ng) of glutamate into either hemisphere. Chicks that had the right eye exposed to light during incubation showed recall of the imprinting stimulus after injection of the left hemisphere but not after injection into the right hemisphere. The reverse was found for chicks that had the left eye exposed to light. Hence, the hemisphere ipsilateral to the eye exposed to light before hatching became essential for recall of imprinting memory. The hemisphere used in recall of imprinting memory received indirect visual inputs and was determined by environmental stimulation (asymmetrical light input).     

破坏狗肾淋巴循环对移植肾影响的实验研究

目的：探讨自体肾移植后淋巴因素对移植肾的影响，为肾移植术是否需要吻合淋巴管提供参考。方法：实验动物为８只成年家犬，开腹，游离并切断左侧肾蒂，置于左髂窝，将肾动脉与左髂内动脉吻合，肾静脉与左髂总静脉吻合，但不吻合淋巴管，右肾作为对照，分别在术后第８、１２、２１天处死动物，用肉眼，光镜和透射电镜观察移植肾的变化。结果：肉眼观，左右肾的大小，颜色，质地无差别，但移植肾与周围组织广泛粘连；光镜：健侧肾皮质肾小管上皮细胞有水样变性，髓质内偶见少量的蛋白和细胞管型。患侧肾除见到与健侧类似的变化外，皮质内偶见脂肪变性，少数肾小球萎缩，部分肾小球代偿性肥大和集合管间质轻度纤维化；电镜：两侧肾小球无明显异常，实验侧近曲小管上皮细胞肿胀，微绒毛排列紊乱，胞浆内空泡增多，线粒体模糊，溶酶体增多，远曲小管和集合管部分上皮细胞坏死。结论：肾移植时可暂不考虑吻合淋巴管     

Devic syndrome: a diagnostic dilemma

Neuromyelitis optica (NMO, also known as Devic syndrome or Devic disease) is a rare clinical entity. Early recognition and prompt treatment can save patients from long-term disability, especially in themonophasic variant of disease. A 24-year-old African American female presented with high-grade fever for 1 day associated with frontal headache, photophobia, and 2 episodes of nonbloody vomiting. She had a history of nonitchy vesicular rash with sudden diminution of vision in the left eye 2 weeks ago. Over the next 24 hours, she developed progressively worsening weakness and numbness in her left arm and left leg, which later involved all limbs. Left eye vision was reduced to light perception with light and accommodation reflexes intact. Lumbar puncture showed lymphocytic pleocytosis with elevated protein. On day 2, neurological examination exhibited quadriparises with hypereflexia and clonus. Magnetic resonance imaging showed diffuse hyperintense signals in the spinal cord in cervical and lumbar regions. An assessment of neuromyelitis optica was made. Anti-NMO antibodies were negative. On day 3, she was intubated because of progressive dyspnea. Plasmapheresis resulted in rapid improvement in respiratory and neurological status. She was extubated on the second day and transferred to floor on day 4. Later, the patient was discharged.     

Morphological asymmetries of the tectum opticum in the pigeon

Pigeons are visually lateralized with a dominance of the right eye. Due to the virtually complete decussation of the optic nerves in birds, a right eye superiority probably depends on a left brain hemisphere dominance. The aim of the present study was to analyze whether morphological asymmetries in the cross-sectional area of perikarya can be found within the retina and the optic tectum. With an image-analyzing system the cross-sectional areas of the somata of retinal ganglion cells and tectal neurons were measured in the left and the right side under blind conditions. The results reveal significant morphological left-right differences, with cells in superficial layers 2–12 being larger on the left side while neurons in laminae 13–15 have larger somata in the right tectum. No retinal asymmetries could be revealed. Since pigeon embryos keep their head turned to the right within the egg, such that the right eye is stimulated by light shining through the shell, it is possible that the morphological asymmetries at the tectal level are induced by left-right differences in prehatching photic stimulation. This embryonic sensory asymmetry might lead to a higher activity level of right eye ganglion cells and to a larger amount of released neurotrophins in the left tectum. This in turn could exert the morphological effects on soma sizes in the superficial retinorecipient layers. Received: 30 January 1997 / Accepted: 9 April 1997     

Non-Paraneoplastic Autoimmune Retinopathy: The First Case Report in Korea

Autoimmune retinopathy (AIR) is an immune-mediated retinopathy, resulting from an immunologic process caused by the aberrant recognition of retinal antigens as autoantigens. The diagnosis of AIR involves the detection of antiretinal antibodies with concurrent clinical and electrophysiological evidence of retinopathy. A 40-year-old patient presented with progressive loss of bilateral vision over several months. A fundus examination was unremarkable. Spectral domain optical coherence tomography revealed a blurred photoreceptor ellipsoid zone at the subfoveal region in both eyes with more prominent disruption in the left eye. Fullfield electroretinography (ERG) showed relatively normal rod and cone responses in the right eye, and decreased photopic bwaves with minimal attenuation of a-waves in the left eye. Multifocal ERG demonstrated slightly reduced amplitude of the inner segment ring in the right eye and decreased amplitudes and delayed latencies of all modalities in the left eye. The patient was suspected to have AIR and it was supported by positive Western blots for 23-kDa protein, enolase (46-kDa), aldolase (40-kDa), 62-kDa and 78-kDa proteins and by immunohistochemical staining of human retinal bipolar and ganglion cells. Despite the immunosuppressive treatment, the destruction of the retinal photoreceptors progressed, and immunosuppressive interventions produced very little visual improvement. We report on what is, to the best of our knowledge, the very first case of serologically confirmed nonparaneoplastic AIR in Korea.     

A case of a mucocele in an Onodi cell.

Onodi cells have been defined as posterior ethmoid cells that have pneumatized laterally and superiorly to the sphenoid sinus. They are often close to the optic nerve or the internal carotid artery. A patient complained of a sudden decrease in left eye visual acuity and left eye pain due to formation of a primary mucocele in an Onodi cell. A coronal computed tomography scan and magnetic resonance imaging were useful for diagnosing the mucocele.     

The coding of perceived eye position

In order to reveal the mechanism of eye position coding, we measured the effect of eye position on assessing the position of a light viewed in a dark environment using a sound as a reference point, before and after adapting to prolonged periods of eccentric viewing (11° right or left). During testing, eye position was varied over ±22°. For each test position, a PEST procedure was used to align the perceived position of a light (with no visual reference points) and a fixed sound source. The perceived position of the light was veridical when looking straight ahead but large and consistent errors were found with eccentric viewing indicating that only about 77% of the eye eccentricity was taken into account, an eye position gain of 0.77, consistent with previous reports. The error was altered by prolonged eccentric viewing. There were two components to this effect: a direction bias and a gain change. The direction bias was symmetric: in a change rather like that induced by prism adaptation, the perceived straight ahead moved in the direction of the previous eccentric viewing. The gain change was asymmetric: after looking to the left, the gain of eye position increased to closer to one (0.77–0.81), in other words the subjects became more accurate. After looking right, the gain of eye position decreased (0.77–0.73): subjects consequently became less accurate. We model these systematic changes in terms of an asymmetric coding system.     

Effect of eye rotation on visual-field map onto superior colliculus and visual cortex

We used multiunit recording to assess the effect of rotating one eye approximately 90 degrees at about the time of normal eye opening. Rotation of the eye did not alter the topography of the retinal maps onto visual cortex or superior colliculus. The intorted eye drove cells at most recording points in the contralateral visual cortex and superior colliculus. In its ipsilateral colliculus the intorted eye drove cells at about 10% of the recording points; that is, the temporal retina of this eye was quite ineffective in driving collicular cells. In its ipsilateral cortex the intorted eye drove cells at about 30% of the recording sites. The unoperated eye drove cells at all locations in both colliculus and cortex on both sides of the brain. The effects of extorsion were studied only in the superior colliculus. Extorsion and intorsion produced similar results except that extorsion produced a less severe deficit in the ability of the temporal retina to drive cells in its ipsilateral colliculus. Cutting all the extraocular muscles without eye rotation was studied only in the colliculus and produced results similar to those produced by intorsion and extorsion. However, the temporal retina of the operated eye was more effective after muscle cut alone than after intorsion or extorsion. Forcing the animal to use the rotated right eye alone on alternate days during the first 3 mo of life did not decrease the deficits. Almost all recording sites in the right colliculus were driven only by the unoperated left eye. If the left eye was sutured when the right eye was rotated, only the right eye drove cells in the left colliculus, but the two eyes were about equally effective in the right colliculus; however, rather few sites in the right colliculus were binocularly driven. We conclude that both extraocular muscle section and eye rotation reduce the effectiveness of the uncrossed input from the operated eye to the superior colliculus and visual cortex. The effects on the superior colliculus are, however, greater.     

Saccade-related and visual activities in the pulvinar nuclei of the behaving rhesus monkey

Summary We studied three subdivisions of the pulvinar: a retinotopically organized inferior area (PI), a retinotopically mapped region of the lateral pulvinar (PL), and a separate, visually responsive component of the lateral pulvinar (Pdm). Single neurons were recorded in these regions from awake, trained rhesus monkeys, and we correlated the discharge patterns of the cells with eye movements. About 60% of the neurons discharged after saccadic eye movements in an illuminated environment and had either excitatory, inhibitory, or biphasic (inhibitory-excitatory) response patterns. These responses were most often transient in nature. Neurons with excitatory activity had a mean onset latency of 72 ms after the termination of the eye movement. Latencies for cells with inhibitory responses averaged 58 ms. In sharp contrast, the cells with biphasic response patterns became active before the termination of the eye movement. A unique set of these neurons termed saccade cells, were active with visually guided eye movements in the light, with the same eye movements made to a briefly pulsed target in the dark, and for similar eye movements made spontaneously in total darkness. The activity was present with the appropriate saccade, independent of the beginning eye position. Biphasic response patterns were typical of these saccade cells. Saccade cells were most common in Pdm and PI. About half of the saccade cells also had some visual response that was independent of eye movement. A second group of cells was active with saccadic eye movements in the light but not in the dark. Some of these cells had clear visual responses that could account for their activity following eye movements; others had no clear visual receptive field. Because of these and other physiological data, we propose that the saccade cells found in Pdm may function in a system dealing with visual spatial attention, while those found in PI may have a role in dealing with the visual consequences of eye movements.     

Primary diffuse large B-cell lymphoma of the ethmoid sinus

Malignant lymphoma of the ethmoid sinus is very rare. A case of diffuse large B-cell lymphoma (DLBCL) of the left ethmoid sinus is presented here. A 79-year-old Japanese man was consulted to our hospital because of head ache and disturbance of left eye movement. Nasal endoscopy revealed a tumor, and imaging modalities including CT and MRI detected a tumor in the left ethmoid sinus. The tumor was invasive into left eye and left nose. A biopsy was performed via the nasal cavity. The biopsy revealed a diffuse proliferation of atypical lymphocytes. The atypical lymphocytes were large and had enlarged hyperchromatic nuclei. Mitotic figures were scattered. Hodgkin's cells were absent. Follicular structures were not seen. Immunohistochemically, the tumor cells were negative for cytokeratins (AE1/2, polyclonal, KL-1, and CAM5.2, Dako) and epithelial membrane antigen, CD3, CD15, CD30, CD45RO, and TdT. In contrast, the tumor cells were positive for CD20, CD45, CD79α, and p53. KI-67 labeling was 100%. Light chain restriction was present; there were numerous λ-chain-positive cells, while κ-chain-positive cells were scant. The pathological diagnosis was DLBCL of the left ethmoid sinus. Imaging of the whole body revealed no tumors and lymphadenopathy other than the ethmoid DLBCL. The patient was treated with chemoradiation, and is now alive 3 months after the presentation. In conclusion, a very rare case of DLBCL of the ethmoid sinus was reported.     

Effects of early monocular deprivation on visual input to cat nucleus of the optic tract

Single cells were recorded extracellularly in the nucleus of the optic tract (NOT) in monocularly deprived cats. Monocular deprivation had no effect on the direction specificity of these neurons, i.e. all cells in the left nucleus preferred movements from right to left and all units in the right nucleus preferred movements from left to right in the visual field. Neurons driven from the deprived eye failed to respond to stimuli moving at velocities above 10 degrees/s whereas neurons driven from the non-deprived eye responded to velocities up to and above 100 degrees/s as do neurons in normal cats. In 8 out of the 10 cats tested all cells in the two nuclei could be influenced only from the contralateral eye irrespective whether this was the deprived or the non-deprived eye. In the other two cats the influence from the non-deprived eye on cells in the ipsilateral NOT was found to be normal. This influence is mediated probably via cortico-fugal projections. In the 8 abnormal cats a clear deprivation effect could be assigned for the first time to the non-deprived eye consisting in a loss of its connections to the ipsilateral NOT. Electrical stimulation of the visual cortex revealed, however, the existence of a connection between the visual cortex and the NOT. A possible explanation for the specific deficit with visual stimulation in the cortico-pretectal synapse ipsilateral to the non-deprived eye is discussed in relation to developmental mechanisms. The conduction velocity of retinal input to the NOT and the output of the NOT to the inferior olive remained uninfluenced by visual deprivation.     

Primary intraocular T-cell-rich large B-cell lymphoma

We report a primary intraocular T-cell-rich large B-cell lymphoma in a 57-year-old woman who underwent 3 diagnostic vitrectomies for a presumed diagnosis of panuveitis. She developed no light perception in the left eye and underwent enucleation. Histopathologic and immunohistochemical studies on the enucleated globe disclosed a primary intraocular large B-cell lymphoma involving the choroid, vitreous, and retina. A large population of T cells was identified among the neoplastic B-cell population. B-cell immunoglobulin gene rearrangement and T-cell receptor gene rearrangement studies using the polymerase chain reaction method indicated that a monoclonal immunoglobulin kappa light chain population was present and that the T-cell population was not monoclonal. This case highlights the importance of interpreting cytologic features in vitreous aspirates in the context of the clinical situation.     

Monocular pattern discrimination in normal and monocularly light-deprived rabbits

Rabbits were trained to discriminate vertical from horizontal striations, mirror image striations and inverted triangles. Each eye was exposed separately to the same patterns. It was found that in many cases the performance with the left and right eye differed considerably. Monocular light deprivation for 3 months after birth did not lead to dominance of the non-deprived eye.     

The parovivirus MVM: particles with altered structural proteins.

Mouse A-9 cells infected with the minute virus of mice were found to have DNA-containing particles of two densities when centrifuged to equilibrium in CsCl, as well as particles which contained no detectable DNA. The DNA-containing heavy particles (1.47 g/cc) were converted to the light particles (1.42 g/cc) after one round of infection when left in the infected cell culture. The light particles had about a fivefold higher hemagglutinating activity than the heavy particles. The only difference in composition detected between the heavy and light particles was in the structural proteins. Sodium dodecyl sulfate (SDS)-polyacrylamide-gel electrophoresis resolved three proteins in the minute virus of mice particles: A protein (92,000 daltons), B protein (72,000 daltons) and C protein (69,000 daltons). The A protein was found in about the same number of molecules in all particles. The empty particles and the heavy particles had B as the major capsid protein, while the light particles had C as the major capsid protein.     

Electron microscopic study on the so-called malignant medullo-epithelioma (ciliary epithelial carcinoma)

Summary A pigeon's-egg-sized tumor arising in the right eye of a 63-year-old man was subjected to light and electron microscopic investigation.The histopathological features were those of medullo-epithelioma, adult type, with tumor cells arranged in alveoli, tubules and papillary projections, and with bone formation. The tumor cells usually had round or ovoid nuclei with prominent nucleoli and a comparatively light cytoplasm. The basement membrane was mostly clear and partly indistinct. Electron microscopically, the tumor cells were partly connected with intermediate junctions; some were light cells, others dark. The light cells, in a younger stage of development, were surrounded by the dark cells with condensed cytoplasm. The tumor cells showed a slight differentiation toward a ciliary epithelium.These findings support the hypothesis that this kind of tumor originates in the ciliary epithelium. We therefore propose calling it a poorly differentiated ciliary epithelial carcinoma.     

Transient asymmetry in the projections of the rostral thalamus to the visual hyperstriatum of the chicken,and reversal of its direction by light exposure

Summary Asymmetry in the visual pathways from the rostral thalamus to the hyperstriatum of the chicken has been found after injecting the retrograde tracer, True Blue (TB), into either the left or right hyperstriatum on day 2 or 12, post-hatching. There are ipsilateral connections from the ventromedial region of the left dorsolateral thalamus, lateral part (DLL) to the left hyperstriatum, and contralateral connections from the left dorsolateral thalamus, rostrolateral part (DLAlr) and the dorsolateral thalamus, dorsal part (DLLd) to the right hyperstriatum. On the right side of the thalamus, the ipsilateral connections from DLL to the right hyperstriatum are present, but there are only very few contralateral connections to the left hyperstriatum. No asymmetry in these pathways is seen in animals injected with TB on day 21. By this age the contralateral connections from the right thalamus to the left hyperstriatum have developed. Thus, the structural asymmetry in these visual pathways is transient, a finding which explains a controversy between two papers published recently in this journal, and which adds considerably to our understanding of the behavioural asymmetries known to occur in the chicken's response to stimuli presented to either the left or right eye. The direction of the asymmetry in visual pathways depends on asymmetrical light input to the eyes of the embryo. Normally the head of the embryo is oriented such that the left eye is occluded. If the head is withdrawn from the egg so that the right eye can be occluded and the left eye exposed to light, the direction of asymmetry in the thalamo-hyperstriatal pathways is reversed. The contralateral connections from the right side of the thalamus (fed by the left eye) to the left hyperstriatum are now present, while those from the left thalamus (fed by the right eye) to the right hyperstriatum are absent. Thus light exposure stimulates the growth of the contralateral connections from the rostral thalamus to hyperstriatum.     

Pseudoneglect and embryonic light stimulation in the avian brain

A bias to allocate attention to the left hemispace, similar to the well-known pseudoneglect phenomenon shown by humans, has been recently reported in domestic chicks and other species of birds. Asymmetrical light exposure of the embryo of the domestic chick in a critical period before hatching is known to be responsible for a structural asymmetry in the visual ascending projections of the thalamofugal pathway and for lateralization of some visual behaviors. Thus the animal model provided by the chick makes possible investigation of the prenatal factors that may influence asymmetry in spatial attention. Here chicks coming from eggs exposed to light (light incubated, Li-chicks) and chicks incubated in darkness (dark incubated, Di-chicks) were tested in a task in which they were required to explore an area in front of them and to sample grains of food. The results showed that Li-chicks attended more to target stimuli located in the left hemispace, whereas no asymmetry was shown by Di-chicks. When grains of food were presented with small novel pebbles as distractors, both Li- and Di-chicks tended to allocate attention toward the left hemispace. When, however, chicks were tested after familiarization with pebbles, no bias was shown by either Li- and Di-chicks. Hence it seems that cerebral lateralization associated with right hemispheric involvement in response to novelty, interacts with the modulatory effect of asymmetric embryonic light stimulation on preferential allocation of spatial attention in the left hemispace (right hemisphere) and right eye (left hemisphere) control of visual discrimination during feeding.     

Orbital position and eye movement influences on visual responses in the pulvinar nuclei of the behaving macaque

Summary We studied the influences of eye movements on the visual responses of neurons in two retinotopically organized areas of the pulvinar of the macaque. Cells were recorded from awake, trained monkeys, and visual responses were characterized immediately before and after the animals made saccadic eye movements. A significant proportion of the cells were more responsive to stimuli around the time of eye movements than they were at other intervals. Other cells had response reduction. For some neurons, the change in excitability was associated with orbital position and not the eye movement. For other cells the change was present with eye movements of similar amplitude and direction but with different starting and ending positions. Here it appears that the eye movement is the important parameter. Other cells had effects related to both eye position and eye movements. In all cells tested, the changes in excitability were present when the experiments were conducted in the dark as well as in the light. This suggests that the mechanism of the effect is related to the eye position or eye movement and not visual-visual interactions. For about half of the neurons with modulations, the response showed facilitation for stimuli presented in the most responsive region of the receptive field but not for those at the edge of the field. For the other cells there was facilitation throughout the field. Thus, a gradient of modulation in the receptive field may vary among cells. These experiments demonstrate modulations of visual responses in the pulvinar by eye movements. Such effects may be part of the visual-behavioral improvements at the end of eye movements and/or contribute to spatial constancy.