Yasuhiro Shinmei

Coding of smooth eye movements in three-dimensional space by frontal cortex

Through the development of a high-acuity fovea, primates with frontal eyes have acquired the ability to use binocular eye movements to track small objects moving in space. The smooth-pursuit system moves both eyes in the same direction to track movement in the frontal plane (frontal pursuit), whereas the vergence system moves left and right eyes in opposite directions to track targets moving towards or away from the observer (vergence tracking). In the cerebral cortex and brainstem, signals related to vergence eye movements—and the retinal disparity and blur signals that elicit them—are coded independently of signals related to frontal pursuit. Here we show that these types of signal are represented in a completely different way in the smooth-pursuit region of the frontal eye fields. Neurons of the frontal eye field modulate strongly during both frontal pursuit and vergence tracking, which results in three-dimensional cartesian representations of eye movements. We propose that the brain creates this distinctly different intermediate representation to allow these neurons to function as part of a system that enables primates to track and manipulate objects moving in three-dimensional space.

Reduction of Intraocular Pressure Using a Modified 360-degree Suture Trabeculotomy Technique in Primary and Secondary Open-Angle Glaucoma: A Pilot Study

PurposeTo investigate the effects of a modified 360-degree suture trabeculotomy technique for primary and secondary open-angle glaucoma (POAG and SOAG). MethodsWe modified the procedure for 360-degree trabeculotomy by using a 5-0 nylon suture, making a scleral flap to allow clear identification of Schlemm canal, and creating a corneal side port incision opposite to the scleral flap to retrieve the suture used to cannulate and cleave the canal. The modified 360-degree suture trabeculotomy (not combined with cataract surgery) was performed on 25 eyes with POAG and 18 eyes with SOAG, and the results were compared retrospectively with those of standard trabeculotomy with metal trabeculotomes (16 eyes with POAG and 19 eyes with SOAG). When the intraocular pressure (IOP) was reduced by 30% from the preoperative IOP and was also below 18 mm Hg at 3, 6, 9, 12, and 18 months after surgery and the patient was taking a similar number or fewer medications, the surgery was considered a “success.” ResultsUsing this modified technique, Schlemm canal was appropriately incised without resistance. At 12 months after the modified 360-degree suture trabeculotomy and trabeculotomy with metal trabeculotomes, the mean postoperative IOP values were 13.1 and 15.2 mm Hg, respectively, and the mean numbers of antiglaucoma medications were 0.5 and 1.4, respectively. The success rates of POAG at 12 months for the modified 360-degree suture trabeculotomy and trabeculotomy with metal trabeculotomes were 84% and 31%, respectively, and those of SOAG were 89% and 50%, respectively. The complications included a transient elevation of the IOP above 30 mm Hg in 22 eyes (47%) treated with the 360-degree suture trabeculotomy and 17 eyes (49%) treated with trabeculotomy with metal trabeculotomes. There was no significant difference between preoperative visual acuity and postoperative visual acuity in either procedure. ConclusionsThis modified 360-degree suture trabeculotomy is a feasible surgical option for POAG and SOAG.

Directional asymmetry in smooth ocular tracking in the presence of visual background in young and adult primates

The smooth pursuit system moves the eyes in space accurately while compensating for visual inputs from the moving background and/or vestibular inputs during head movements. To understand the mechanisms underlying such interactions, we examined the influence of a stationary textured visual background on smooth pursuit tracking and compared the results in young and adult humans and monkeys. Six humans (three children, three adults) and six macaque monkeys (five young, one adult) were used. Human eye movements were recorded using infrared oculography and evoked by a sinusoidally moving target presented on a computer monitor. Scleral search coils were used for monkeys while they tracked a target presented on a tangent screen. The target moved in a sinusoidal or trapezoidal fashion with or without whole body rotation in the same plane. Two kinds of backgrounds, homogeneous and stationary textured, were used. Eye velocity gains (eye velocity/target velocity) were calculated in each condition to compare the influence of the textured background. Children showed asymmetric eye movements during vertical pursuit across the textured (but not the homogeneous) background; upward pursuit was severely impaired, and consisted mostly of catch-up saccades. In contrast, adults showed no asymmetry during pursuit across the different backgrounds. Monkeys behaved similarly; only slight effects were observed with the textured background in a mature monkey, whereas upward pursuit was severely impaired in young monkeys. In addition, VOR cancellation was severely impaired during upward eye and head movements, resulting in residual downward VOR in young monkeys. From these results, we conclude that the directional asymmetry observed in young primates may reflect a different neural organization of the vertical, particularly upward, pursuit system in the face of conflicting visual and vestibular inputs that can be associated with pursuit eye movements. Apparently, proper compensation matures later.

Correlation between decreased choroidal blood flow velocity and the pathogenesis of acute zonal occult outer retinopathy.

To evaluate changes of choroidal circulation quantitatively using laser speckle flowgraphy in patients with acute zonal occult outer retinopathy.

Role of the frontal eye fields in smooth-gaze tracking

Visual and vestibular senses are essential for appropriate motor behavior in three-dimensional (3D) space. Discovery of relevant specific subdivisions in sensory and motor pathways in recent decades has considerably advanced our understanding of the overall neural control of movement. Such subdivisions must eventually be further delineated into functional neural circuits for purposeful motor acts. Two critical questions are where in the brain do such circuits operate, and by what means. In this chapter, these issues are addressed for smooth tracking eye-movement systems in the simian. These results show that contrary to current understanding, synthesis of the functionally similar eye-movement systems, smooth-pursuit and vergence, takes place in the frontal cortex. This processing, which is of higher order than previously supposed, enables primates to track and manipulate objects moving in 3D space with the utmost of efficiency.

Mydriasis with Light-Near Dissociation in Fisher's Syndrome

BackgroundApproximately 50% of patients with Fishers syndrome show involvement of the pupillomotor fibers and present with mydriasis and light-near dissociation. However, it is uncertain whether this phenomenon is induced by an aberrant reinnervation mechanism as in tonic pupil, or is based on other mechanisms such as those associated with tectal pupils.CasesWe evaluated the clinical course and the pupillary responses in four of 27 patients with Fishers syndrome who presented with bilateral mydriasis.ObservationsThe pupils of both eyes of the four patients were involved at the early stage of Fishers syndrome. The pupils in patients 1 and 2 showed mydriasis with apparent light-near dissociation lasting for a significant period and had denervation supersensitivity to cholinergic agents. On the other hand, the pupils of patients 3 and 4 were dilated and fixed to both light and near stimuli.ConclusionsOur observations indicate that the denervated iris sphincter muscles, which are supersensitive to the cholinergic transmitter, may play an important role in the expression of light-near dissociation in Fishers syndrome. Jpn J Ophthalmol 2007;51:224–227

Ocular motor disorders in mitochondrial encephalopathy with lactic acid and stroke-like episodes with the 3271 (T-C) point mutation in mitochondrial DNA.

Background: Ocular motor function can provide insights into areas of dysfunction within the nervous system. There are no published eye movement recordings in patients with mitochondrial encephalopathy with lactic acid and stroke-like episodes (MELAS). Our purpose in this study was to analyze the ocular motor features of a family with MELAS with a (T-C) mutation at nucleotide position 3271 in the mitochondrial tRNA-Leu gene. Methods: The search coil method was used to record visually-guided saccades, antisaccades, and triangular pursuit tasks in the horizontal and vertical planes in three patients in a Japanese family with MELAS. Results: The patients showed saccadic dysmetria and prolonged saccadic reaction times, deficits in the ability to suppress reflex eye movements, and increased reaction time during antisaccades, downbeat nystagmus, square wave jerks, and impairment in pursuit. Conclusions: On the basis of eye movement recordings, patients with MELAS have frontal cortex as well as cerebellar dysfunction.

Adaptive eye movements induced by cross-axis pursuit--vestibular interactions in trained monkeys.

We showed previously that smooth pursuit training combined with whole-body rotation in the orthogonal plane induces adaptive cross-axis vestibulo-ocular reflex (VOR). To gain an insight into the possible pathways and the nature of error signals for cross-axis VOR adaptation, we examined further properties of adaptive responses. In the first series, we trained monkeys for vertical pursuit during sinusoidal yaw rotation at 0.5 Hz ( - 10°) by presenting a target spot either in phase with, or with phase shifts (lead or lag) of 90° to, the chair for 1 h. After training, sinusoidal or trapezoidal yaw rotation was tested in complete darkness without a target. Different training conditions resulted in different amounts of phase shift in cross-axis VOR. Trapezoidal yaw rotation (peak acceleration , 780°/s 2 ) revealed further differences in the direction, latency and time course of the adaptive responses depending on the conditions of the pursuit task. At least two (fast and slow) components with different latencies were induced in the cross-axis VOR by trapezoidal rotation after in-phase and phase-shift training. Adaptive responses were accurately simulated by the weighted sum of these two components. In the second series, we examined the effects of sequentially flashed (10 w s) targets in the horizontal plane during pitch rotation. The monkeys learned to track such targets by smooth pursuit, and cross-axis VOR was also induced after such apparent motion stimuli without retinal slip of the target image. These results indicate the importance of eye velocity for cross-axis VOR and suggest that this adaptation occurs most probably in the smooth pursuit pathways.We showed previously that smooth pursuit training combined with whole-body rotation in the orthogonal plane induces adaptive cross-axis vestibulo-ocular reflex (VOR). To gain an insight into the possible pathways and the nature of error signals for cross-axis VOR adaptation, we examined further properties of adaptive responses. In the first series, we trained monkeys for vertical pursuit during sinusoidal yaw rotation at 0.5 Hz (+/- 10 degrees) by presenting a target spot either in phase with, or with phase shifts (lead or lag) of 90 degrees to, the chair for 1 h. After training, sinusoidal or trapezoidal yaw rotation was tested in complete darkness without a target. Different training conditions resulted in different amounts of phase shift in cross-axis VOR. Trapezoidal yaw rotation (peak acceleration approximately 780 degrees/s2) revealed further differences in the direction, latency and time course of the adaptive responses depending on the conditions of the pursuit task. At least two (fast and slow) components with different latencies were induced in the cross-axis VOR by trapezoidal rotation after in-phase and phase-shift training. Adaptive responses were accurately simulated by the weighted sum of these two components. In the second series, we examined the effects of sequentially flashed (10 microseconds) targets in the horizontal plane during pitch rotation. The monkeys learned to track such targets by smooth pursuit, and cross-axis VOR was also induced after such apparent motion stimuli without retinal slip of the target image. These results indicate the importance of eye velocity for cross-axis VOR and suggest that this adaptation occurs most probably in the smooth pursuit pathways.

Effect of geranylgeranylacetone on the protection of retinal ganglion cells in a mouse model of normal tension glaucoma

Glaucoma is characterized by axonal degeneration of retinal ganglion cells (RGCs) and apoptotic death of their cell bodies, and lowering intraocular pressure is associated with an attenuation of progressive optic nerve damage. Nevertheless, intraocular pressure (IOP) reduction alone was not enough to inhibit the progression of disease, which suggests the contribution of other factors to the glaucoma pathogenesis. In this study, we investigated the cytoprotective effect of geranylgeranylacetone (GGA) on RGCs degeneration using a normal tension glaucoma (NTG) mouse model, which lacks glutamate/aspartate transporter (GLAST) and demonstrates spontaneous RGC and optic nerve degeneration without elevated intraocular pressure (IOP). Three-week-old GLAST+/− mice were given oral administration of GGA at 100, 300, or 600 mg/kg/day or vehicle alone, and littermate control mice were given vehicle alone for 14 days, respectively. At 5 weeks after birth, the number of RGCs was counted in paraffin sections of retinal tissues stained with hematoxylin and eosin. In addition, retrograde labeling technique was also used to quantify the number of RGC. Expression and localization of heat shock protein 70 (HSP70) in retinas were evaluated by reverse transcription polymerase chain reaction and immunohistochemistry, respectively. Activities of caspase-9 and -3 in retinas were also assessed. The number of RGCs of GLAST+/− mice significantly decreased, as compared to that of control mice. RGC loss was significantly suppressed by administration of GGA at 600 mg/kg/day, compared with vehicle alone. Following GGA administration, HSP70 was significantly upregulated together with reduction in the activities of caspase-9 and -3. Our studies highlight HSP70 induction in the retina is available to suppress RGC degeneration, and thus GGA may be applicable for NTG as a promising therapy.

Central serous retinal detachment detected by optical coherence tomography in Leber's idiopathic stellate neuroretinitis.

Lebers idiopathic stellate neuroretinitis (LISN) is characterized mainly by bifocal lesions, namely, optic neuritis and maculopathy with starlike exudates. However, it is unclear how the macular region is involved. 1 - 4 In our patient with LISN, optical coherence tomography (OCT) revealed central serous retinal detachment with exudates in the retinal outer plexiform layer.