Clinical value of video oculomotor evaluation in the differential diagnosis of multiple system atrophy and Parkinson's disease.

BACKGROUND: Multiple system atrophy (MSA) is a neurodegenerative disease that progresses rapidly and has a poor prognosis. This study aimed to assess the value of video oculomotor evaluation (VOE) in the differential diagnosis of MSA and Parkinson's disease (PD). METHODS: In total, 28 patients with MSA, 31 patients with PD, and 30 age- and sex-matched healthy controls (HC) were screened and included in this study. The evaluation consisted of a gaze-holding test, smooth pursuit eye movement (SPEM), random saccade, and optokinetic nystagmus (OKN). RESULTS: The MSA and PD groups had more abnormalities and decreased SPEM gain than the HC group (64.29%, 35.48%, 10%, p < .001). The SPEM gain in the MSA group was significantly lower than that in the PD group at specific frequencies. Patients with MSA and PD showed prolonged latencies in all saccade directions compared with those with HC. However, the two diseases had no significant differences in the saccade parameters. The OKN gain gradually decreased from the HC to the PD and the MSA groups (p < .05). Compared with the PD group, the gain in the MSA group was further decreased in the OKN test at 30°/s (Left, p = .010; Right p = .016). Receiver operating characteristic curves showed that the combination of oculomotor parameters with age and course of disease could aid in the differential diagnosis of patients with MSA and PD, with a sensitivity of 89.29% and a specificity of 70.97%. CONCLUSIONS: The combination of oculomotor parameters and clinical data may aid in the differential diagnosis of MSA and PD. Furthermore, VOE is vital in the identification of neurodegenerative diseases.

PyOKR: A Semi-Automated Method for Quantifying Optokinetic Reflex Tracking Ability.

The study of behavioral responses to visual stimuli is a key component of understanding visual system function. One notable response is the optokinetic reflex (OKR), a highly conserved innate behavior necessary for image stabilization on the retina. The OKR provides a robust readout of image tracking ability and has been extensively studied to understand visual system circuitry and function in animals from different genetic backgrounds. The OKR consists of two phases: a slow tracking phase as the eye follows a stimulus to the edge of the visual plane and a compensatory fast phase saccade that resets the position of the eye in the orbit. Previous methods of tracking gain quantification, although reliable, are labor intensive and can be subjective or arbitrarily derived. To obtain more rapid and reproducible quantification of eye tracking ability, we have developed a novel semi-automated analysis program, PyOKR, that allows for quantification of two-dimensional eye tracking motion in response to any directional stimulus, in addition to being adaptable to any type of video-oculography equipment. This method provides automated filtering, selection of slow tracking phases, modeling of vertical and horizontal eye vectors, quantification of eye movement gains relative to stimulus speed, and organization of resultant data into a usable spreadsheet for statistical and graphical comparisons. This quantitative and streamlined analysis pipeline, readily accessible via PyPI import, provides a fast and direct measurement of OKR responses, thereby facilitating the study of visual behavioral responses.

Alertness and Visual Attention Impact Different Aspects of the Optokinetic Reflex.

Purpose: Assessing visual attention and alertness is of great importance in visual and cognitive neuroscience, providing objective measures valuable for both researchers and clinicians. This study investigates how the optokinetic response differs between levels of visual attention in healthy adults while controlling for alertness. Methods: Twelve healthy subjects (8 men and 4 women; mean age = 33 ± 9.36) with intact gaze-stability, visual acuity, and binocularity were recruited. Subjects viewed a rotating visual scene provoking torsional optokinetic nystagmus (OKN) while wearing a video eye tracker in a seated head-fixed position. Tasks requiring focused, neutral, and divided visual attention were issued to each subject and the OKN was recorded. Pupil sizes were monitored as a proxy for alertness. Results: Pupil dilation was increased for both focused and divided visual attention. The number of nystagmus beats was highest for the focused condition and lowest for the divided attentional task. OKN gain was increased during both focused and divided attention. The distribution of nystagmus beats over time showed that only focused attention produced a reliable adaptation of the OKN. Conclusions: Results consequently indicate that OKN frequency is adaptive to a viewer's level of visual attention, whereas OKN gain is influenced by alertness levels. This pattern offers insight into the neural processes integrating visual input with reflexive motor responses. For example, it contextualizes why attention to visual stimuli can cause dizziness, as the OKN frequency reflects activity of the velocity storage mechanism. Additionally, the OKN could offer a possible venue for differentiating between visual attention and alertness during psychometric testing.

Customised vestibular rehabilitation with the addition of virtual reality based therapy in the management of persistent postural-perceptual dizziness.

OBJECTIVE: Visual-vestibular mismatch patients experience persistent postural and perceptual dizziness. Previous studies have shown the benefit of vestibular rehabilitation for visual desensitisation using gaze stabilisation exercises and optokinetic stimulation. This study assessed the benefit of customised vestibular rehabilitation with visual desensitisation and virtual reality based therapy rehabilitation in the management of patients with persistent postural-perceptual dizziness. METHODS: This retrospective study included 100 patients with Situational Characteristic Questionnaire scores of more than 0.9. All patients received virtual reality based therapy along with usual vestibular rehabilitation using gaze stabilisation exercises with a plain background followed by graded visual stimulation and optokinetic digital video disc stimulation. Patients' symptoms were assessed before and after vestibular rehabilitation using the Situational Characteristic Questionnaire, Generalised Anxiety Disorder Assessment-7, Nijmegen Questionnaire and Dizziness Handicap Inventory. RESULTS: There were statistically significant improvements in Situational Characteristic Questionnaire scores, Nijmegen Questionnaire scores and Dizziness Handicap Inventory total score. However, there was a statistically insignificant difference in Generalised Anxiety Disorder Assessment-7 scores. There was a significant positive correlation between post-rehabilitation Situational Characteristic Questionnaire scores and other questionnaire results. CONCLUSION: Incorporating virtual reality based therapy with customised vestibular rehabilitation exercises results in significant improvement in persistent postural-perceptual dizziness related symptoms.

Spherical arena reveals optokinetic response tuning to stimulus location, size, and frequency across entire visual field of larval zebrafish.

Many animals have large visual fields, and sensory circuits may sample those regions of visual space most relevant to behaviours such as gaze stabilisation and hunting. Despite this, relatively small displays are often used in vision neuroscience. To sample stimulus locations across most of the visual field, we built a spherical stimulus arena with 14,848 independently controllable LEDs. We measured the optokinetic response gain of immobilised zebrafish larvae to stimuli of different steradian size and visual field locations. We find that the two eyes are less yoked than previously thought and that spatial frequency tuning is similar across visual field positions. However, zebrafish react most strongly to lateral, nearly equatorial stimuli, consistent with previously reported spatial densities of red, green, and blue photoreceptors. Upside-down experiments suggest further extra-retinal processing. Our results demonstrate that motion vision circuits in zebrafish are anisotropic, and preferentially monitor areas with putative behavioural relevance.

Embryonic stem cell-derived photoreceptor precursor cells differentiated by coculture with RPE cells.

Purpose: To describe the derivation of photoreceptor precursor cells from human embryonic stem cells by coculture with RPE cells. Methods: Human embryonic stem cells were induced to differentiate into neural precursor cells and then cocultured with RPE cells to obtain cells showing retinal photoreceptor features. Immunofluorescent staining, reverse transcription-PCR (RT-PCR), and microarray analysis were performed to identify photoreceptor markers, and a cGMP assay was used for in vitro functional analysis. After subretinal injection in rat animal models, retinal function was determined with electroretinography and optokinetic response detection, and immunofluorescent staining was performed to assess the survival of the injected cells. Results: Cocultured cells were positive for rhodopsin, red and blue opsin, recoverin, and phosphodiesterase 6 beta on immunofluorescent staining and RT-PCR. Serial detection of stem cell-, neural precursor-, and photoreceptor-specific markers was noted in each stage of differentiation with microarray analysis. Increased cGMP hydrolysis in light-exposed conditions compared to that in dark conditions was observed. After the subretinal injection in the rats, preservation of optokinetic responses was noted up to 20 weeks, while electroretinographic response decreased. Survival of the injected cells was confirmed with positive immunofluorescence staining of human markers at 8 weeks. Conclusions: Cells showed photoreceptor-specific features when stem cell-derived neurogenic precursors were cocultured with RPE cells.

Correcting QUEST Magnetic Resonance Imaging-Sensitive Free Radical Production in the Outer Retina In Vivo Does Not Correct Reduced Visual Performance in 24-Month-Old C57BL/6J Mice.

Purpose: To test the hypothesis that acutely correcting a sustained presence of outer retina free radicals measured in vivo in 24-month-old mice corrects their reduced visual performance. Methods: Male C57BL/6J mice two and 24 months old were noninvasively evaluated for unremitted production of paramagnetic free radicals based on whether 1/T1 in retinal laminae are reduced after acute antioxidant administration (QUEnch-assiSTed [QUEST] magnetic resonance imaging [MRI]). Superoxide production was measured in freshly excised retina (lucigenin assay). Combining acute antioxidant administration with optical coherence tomography (i.e., QUEST OCT) tested for excessive free radical-induced shrinkage of the subretinal space volume. Combining antioxidant administration with optokinetic tracking tested for a contribution of uncontrolled free radical production to cone-based visual performance declines. Results: At two months, antioxidants had no effect on 1/T1 in vivo in any retinal layer. At 24 months, antioxidants reduced 1/T1 only in superior outer retina. No age-related change in retinal superoxide production was measured ex vivo, suggesting that free radical species other than superoxide contributed to the positive QUEST MRI signal at 24 months. Also, subretinal space volume did not show evidence for age-related shrinkage and was unresponsive to antioxidants. Finally, visual performance declined with age and was not restored by antioxidants that were effective per QUEST MRI. Conclusions: An ongoing uncontrolled production of outer retina free radicals as measured in vivo in 24 mo C57BL/6J mice appears to be insufficient to explain reductions in visual performance.

Pupil response is modulated with optokinetic nystagmus in transparent motion.

When two visual patterns moving in opposite directions are superimposed on the same depth plane, they appear to have two transparent surfaces moving independently (transparent motion). Additionally, the direction of the slow phase of optokinetic nystagmus (OKN) corresponds to the direction of motion that dominates the perceptual appearance. This study examines whether pupil changes correspond to the luminance of the dominated objects related to the transition of the slow-phase direction in OKN following objects. Stimuli consisted of two random dot patterns of different luminance that moved in opposite directions. The results showed that pupil size changed in accordance with the luminance of the pattern in the slow phase of OKN immediately after OKN transition. This suggests that pupil size is modulated with OKN in transparent motion.

Eye movement patterns in Iranian dyslexic children compared to non-dyslexic children.

OBJECTIVE: Dyslexia is the most common learning disorder that affects 5-10% of school aged children. Eye movement abnormalities and visual processing deficits have been reported in some of dyslexic children. Objective of this study is to compare the eye-movement patterns of Iranian dyslexic children with those of non-dyslexic children as they perform the oculomotor tests and to explore the relationship between their eye-movement patterns and their reading ability. METHODS: Binocular eye movements were recorded by oculomotor subtype of videonystagmography (VNG) testing on 30 dyslexic children and 20 non-dyslexic age-matched children (aged 8-12) in both genders. Dyslexic children were diagnosed with DSM-V scale by experts in reading disorder centers. Gain of the pursuit and optokinetic tests and the latency, accuracy and velocity of the saccade test were measured in both groups of dyslexic and non-dyslexic children. The independent samples t-test, Chi-square test and linear regression test in SPSS v. 21 were used to analyze behavioral and eye-movement parameters. RESULTS: Compared to the non-dyslexic group, dyslexic children presented lower gain in pursuit and optokinetic tests, and increased latency with decreased accuracy in saccade test. All behavioral and eye-movement parameters without saccade velocity differed significantly among two groups. CONCLUSION: The atypical eye movement patterns observed in dyslexic children suggests a deficiency in the visual information processing and an immaturity of brain structures responsible for oculomotor skills.

Effect of diverse recoding of granule cells on optokinetic response in a cerebellar ring network with synaptic plasticity.

We consider a cerebellar ring network for the optokinetic response (OKR), and investigate the effect of diverse recoding of granule (GR) cells on OKR by varying the connection probability pc from Golgi to GR cells. For an optimal value of pc∗(=0.06), individual GR cells exhibit diverse spiking patterns which are in-phase, anti-phase, or complex out-of-phase with respect to their population-averaged firing activity. Then, these diversely-recoded signals via parallel fibers (PFs) from GR cells are effectively depressed by the error-teaching signals via climbing fibers from the inferior olive which are also in-phase ones. Synaptic weights at in-phase PF-Purkinje cell (PC) synapses of active GR cells are strongly depressed via strong long-term depression (LTD), while those at anti-phase and complex out-of-phase PF-PC synapses are weakly depressed through weak LTD. This kind of "effective" depression (i.e., strong/weak LTD) at the PF-PC synapses causes a big modulation in firings of PCs, which then exert effective inhibitory coordination on the vestibular nucleus (VN) neuron (which evokes OKR). For the firing of the VN neuron, the learning gain degree Lg, corresponding to the modulation gain ratio, increases with increasing the learning cycle, and it saturates at about the 300th cycle. By varying pc from pc∗, we find that a plot of saturated learning gain degree Lg∗ versus pc forms a bell-shaped curve with a peak at pc∗ (where the diversity degree in spiking patterns of GR cells is also maximum). Consequently, the more diverse in recoding of GR cells, the more effective in motor learning for the OKR adaptation.

Long term visuo-vestibular mismatch in freely behaving mice differentially affects gaze stabilizing reflexes.

The vestibulo-ocular reflex (VOR) and the optokinetic reflex (OKR) work synergistically to stabilize gaze in response to head movements. We previously demonstrated that a 14-day visuo-vestibular mismatch (VVM) protocol applied in freely behaving mice decreased the VOR gain. Here, we show for the first time that the OKR gain is also reduced and report on the recovery dynamics of both VOR and OKR after the end of the VVM protocol. Using sinusoidally-modulated stimulations, the decreases in VOR and OKR were found to be frequency-selective with larger reductions for frequencies < 0.5 Hz. Constant-velocity OKR stimulation tests demonstrated that the persistent components of the OKR were not modified while the transient, initial responses were. To identify the signals driving VOR and OKR reductions, we compared the responses of mice exposed to a high-contrast and no-contrast VVM. Despite being more robust in the high-contrast conditions, reductions were largely comparable and recovered with a similar time course. An analysis that directly compared VOR and OKR responses revealed that, alterations in the VOR were of significantly larger amplitude with significantly slower dynamics of recovery. Our findings are evidence for a frequency-selective influence of visual signals in the tuning of gaze stabilizing reflexes in normal mice.

Rods Contribute to Visual Behavior in Larval Zebrafish.

Purpose: Although zebrafish rods begin to develop as early as 2 days postfertilization (dpf), they are not deemed anatomically mature and functional until 15 to 21 dpf. A recent study detected a small electroretinogram (ERG) from rods in a cone mutant called no optokinetic response f (nof) at 5 dpf, suggesting that young rods are functional. Whether they can mediate behavioral responses in larvae is unknown. Methods: We first confirmed rod function by measuring nof ERGs under photopic and scotopic illumination at 6 dpf. We evaluated the role of rods in visual behaviors using two different assays: the visual-motor response (VMR) and optokinetic response (OKR). We measured responses from wild-type (WT) larvae and nof mutants under photopic and scotopic illuminations at 6 dpf. Results: Nof mutants lacked a photopic ERG. However, after prolonged dark adaptation, they displayed scotopic ERGs. Compared with WT larvae, the nof mutants displayed reduced VMRs. The VMR difference during light onset gradually diminished with decreased illumination and became nearly identical at lower light intensities. Additionally, light-adapted nof mutants did not display an OKR, whereas dark-adapted nof mutants displayed scotopic OKRs. Conclusions: Because the nof mutants lacked a photopic ERG but displayed scotopic ERGs after dark adaptation, the mutants clearly had functional rods. WT larvae and the nof mutants displayed comparable scotopic light-On VMRs and scotopic OKRs after dark adaptation, suggesting that these responses were driven primarily by rods. Together, these observations indicate that rods contribute to zebrafish visual behaviors as early as 6 dpf.

Neuroretinal-Derived Caveolin-1 Promotes Endotoxin-Induced Inflammation in the Murine Retina.

Purpose: The immune-privileged environment and complex organization of retinal tissue support the retina's essential role in visual function, yet confound inquiries into cell-specific inflammatory effects that lead to dysfunction and degeneration. Caveolin-1 (Cav1) is an integral membrane protein expressed in several retinal cell types and is implicated in immune regulation. However, whether Cav1 promotes or inhibits inflammatory processes in the retina (as well as in other tissues) remains unclear. Previously, we showed that global-Cav1 depletion resulted in reduced retinal inflammatory cytokine production but paradoxically elevated retinal immune cell infiltration. We hypothesized that these disparate responses are the result of differential cell-specific Cav1 functions in the retina. Methods: We used Cre/lox technology to deplete Cav1 specifically in the neural retinal (NR) compartment to clarify the role NR-specific Cav1 (NR-Cav1) in the retinal immune response to intravitreal inflammatory challenge induced by activation of Toll-like receptor-4 (TLR4). We used multiplex protein suspension array and flow cytometry to evaluate innate immune activation. Additionally, we used bioinformatics assessment of differentially expressed membrane-associated proteins to infer relationships between NR-Cav1 and immune response pathways. Results: NR-Cav1 depletion, which primarily affects Müller glia Cav1 expression, significantly altered immune response pathway regulators, decreased retinal inflammatory cytokine production, and reduced retinal immune cell infiltration in response to LPS-stimulated inflammatory induction. Conclusions: Cav1 expression in the NR compartment promotes the innate TLR4-mediated retinal tissue immune response. Additionally, we have identified novel potential immune modulators differentially expressed with NR-Cav1 depletion. This study further clarifies the role of NR-Cav1 in retinal inflammation.

Optokinetic stimulation induces vertical vergence, possibly through a non-visual pathway.

Vertical vergence is generally associated with one of three mechanisms: vestibular activation during a head tilt, induced by vertical visual disparity, or as a by-product of ocular torsion. However, vertical vergence can also be induced by seemingly unrelated visual conditions, such as optokinetic rotations. This study aims to investigate the effect of vision on this latter form of vertical vergence. Eight subjects (4m/4f) viewed a visual scene in head erect position in two different viewing conditions (monocular and binocular). The scene, containing white lines angled at 45° against a black background, was projected at an eye-screen distance of 2 m, and rotated 28° at an acceleration of 56°/s2. Eye movements were recorded using a Chronos Eye-Tracker, and eye occlusions were carried out by placing an infrared-translucent cover in front of the left eye during monocular viewing. Results revealed vergence amplitudes during binocular viewing to be significantly lower than those seen for monocular conditions (p = 0.003), while torsion remained unaffected. This indicates that vertical vergence to optokinetic stimulation, though visually induced, is visually suppressed during binocular viewing. Considering that vertical vergence is generally viewed as a vestibular signal, the findings may reflect a visually induced activation of a vestibular pathway.

Suppressive control of optokinetic and vestibular nystagmus by the primate frontal eye field.

When the eyes are fixated on a spot, fixation neurons in the frontal eye field (FEF) show an increase in activity. Our previous study suggested that fixation neurons in the FEF contribute to the suppression of saccades and smooth pursuit eye movements to maintain active fixation. The present study examined the role of the FEF in the suppressive control of reflexive eye movements, optokinetic and vestibular nystagmus, in trained monkeys. Electrical stimulation in the FEF suppressed the quick and slow phases of optokinetic and vestibular nystagmus at an intensity lower than the threshold for eliciting electrically evoked saccades. Relatively weak suppression influenced the slow phase of vestibular nystagmus. During optokinetic or vestibular nystagmus, presentation of a stationary small spot to the eyes followed by fixation is known to suppress both the quick and slow phases of eye movements. We recorded the activity of fixation neurons in the FEF and found that fixation neurons usually showed a decrease in activity during optokinetic and vestibular nystagmus and an increase in activity during the suppression of nystagmus by visual fixation. The present results show that the activity of fixation neurons in the FEF is related to the suppressive control of optokinetic and vestibular nystagmus for maintaining active fixation. We discuss the role of a generalized visual fixation system that can maintain visual attention on an interesting object.NEW & NOTEWORTHY In this study, electrical stimulation in the frontal eye field (FEF) suppressed the quick and slow phases of optokinetic and vestibular nystagmus at an intensity subthreshold for eliciting saccades. Furthermore, the activity of fixation neurons in the FEF was related to the suppression of optokinetic and vestibular nystagmus by visual fixation. This suggests that a common neuronal assembly in the FEF may contribute to the suppressive control of different functional classes of eye movements.

Vertical Optokinetic Stimulation Induces Diagonal Eye Movements in Patients with Idiopathic Infantile Nystagmus.

Purpose: In patients with early ocular misalignment and nystagmus, vertical optokinetic stimulation reportedly increases the horizontal component of the nystagmus present during fixation, resulting in diagonal eye movements. We tested patients with infantile nystagmus syndrome but normal ocular alignment to determine if this crosstalk depends on strabismus. Methods: Eye movements were recorded in seven patients with infantile nystagmus. All but one patient had normal ocular alignment with high-grade stereopsis. Nystagmus during interleaved trials of right, left, up, and down optokinetic stimulation was compared with waveforms recorded during fixation. Six patients with strabismus but no nystagmus were also tested. Results: In infantile nystagmus syndrome, horizontal motion evoked a mostly jerk nystagmus with virtually no vertical component. A vertical optokinetic pattern produced nystagmus with a diagonal trajectory. It was not simply a combination of a vertical component from optokinetic stimulation and a horizontal component from the subject's congenital nystagmus, rather in six of seven patients, the slow-phase velocity of the horizontal component during vertical optokinetic stimulation differed from that recorded during fixation. In the six strabismus patients without nystagmus, responses to vertical optokinetic stimulation were normal. Conclusions: In patients with congenital motor nystagmus, a vertical noise pattern drives a diagonal nystagmus. This appears to arise because of crosstalk between the vertical and horizontal components of the optokinetic system. This abnormal response to vertical stimulation is not caused by strabismus because it occurs in patients with infantile nystagmus without strabismus. Moreover, it is absent in patients with strabismus and no spontaneous nystagmus.

Velocity storage mechanism drives a cerebellar clock for predictive eye velocity control.

Predictive motor control is ubiquitously employed in animal kingdom to achieve rapid and precise motor action. In most vertebrates large, moving visual scenes induce an optokinetic response (OKR) control of eye movements to stabilize vision. In goldfish, the OKR was found to be predictive after a prolonged exposure to temporally periodic visual motion. A recent study showed the cerebellum necessary to acquire this predictive OKR (pOKR), but it remained unclear as to whether the cerebellum alone was sufficient. Herein we examined different fish species known to share the basic architecture of cerebellar neuronal circuitry for their ability to acquire pOKR. Carps were shown to acquire pOKR like goldfish while zebrafish and medaka did not, demonstrating the cerebellum alone not to be sufficient. Interestingly, those fish that acquired pOKR were found to exhibit long-lasting optokinetic after nystagmus (OKAN) as opposed to those that didn't. To directly manipulate OKAN vestibular-neurectomy was performed in goldfish that severely shortened OKAN, but pOKR was acquired comparable to normal animals. These results suggest that the neuronal circuitry producing OKAN, known as the velocity storage mechanism (VSM), is required to acquire pOKR irrespective of OKAN duration. Taken together, we conclude that pOKR is acquired through recurrent cerebellum-brainstem parallel loops in which the cerebellum adjusts VSM signal flow and, in turn, receives appropriately timed eye velocity information to clock visual world motion.

Immunization Against Oxidized Elastin Exacerbates Structural and Functional Damage in Mouse Model of Smoke-Induced Ocular Injury.

Purpose: Age-related macular degeneration (AMD) is the leading cause of blindness in Western populations. While an overactive complement system has been linked to pathogenesis, mechanisms contributing to its activation are largely unknown. In aged and AMD eyes, loss of the elastin layer (EL) of Bruch's membrane (BrM) has been reported. Elastin antibodies are elevated in patients with AMD, the pathogenic significance of which is unclear. Here we assess the role of elastin antibodies using a mouse model of smoke-induced ocular pathology (SIOP), which similarly demonstrates EL loss. Methods: C57BL/6J mice were immunized with elastin or elastin peptide oxidatively modified by cigarette smoke (ox-elastin). Mice were then exposed to cigarette smoke or air for 6 months. Visual function was assessed by optokinetic response, retinal morphology by spectral-domain optical coherence tomography and electron microscopy, and complement activation and antibody deposition by Western blot. Results: Ox-elastin IgG and IgM antibodies were elevated in ox-elastin immunized mice following 6 months of smoke, whereas elastin immunization had a smaller effect. Ox-elastin immunization exacerbated smoke-induced vision loss, with thicker BrM and more damaged retinal pigment epithelium (RPE) mitochondria compared with mice immunized with elastin or nonimmunized controls. These changes were correlated with increased levels of IgM, IgG2, IgG3, and complement activation products in RPE/choroid. Conclusions: These data demonstrate that SIOP mice generate elastin-specific antibodies and that immunization with ox-elastin exacerbates ocular pathology. Elastin antibodies represented complement fixing isotypes that, together with the increased presence of complement activation seen in immunized mice, suggest that elastin antibodies exert pathogenic effects through mediating complement activation.

Effects of prolonged roll-tilt on the subjective visual and haptic vertical in healthy human subjects.

BACKGROUND: While verticality perception is normally accurate when upright, a systematic bias ("post-tilt bias") is seen after prolonged roll-tilt. The source of the bias could either be central (shifting "null" position) or related to changes in torsional eye-position. OBJECTIVE: To study the mechanisms of the post-tilt bias in vision-dependent and vision-independent paradigms and to characterize the impact of optokinetic stimulation. METHODS: The subjective visual-vertical (SVV) and subjective haptic-vertical (SHV) were measured after static roll-tilt (±90deg ear-down ("adaptation") position; duration = 5 min; n = 9 subjects). To assess the effect of visual stimuli, a control condition (darkness) was compared with an optokinetic stimulus (clockwise/counter-clockwise rotation, 60deg/sec) during adaptation. RESULTS: A significant post-tilt bias was more frequent for the SVV than the SHV (72% vs. 54%, p = 0.007) with shifts pointing towards or away from the adaptation position with similar frequency. Exponential-decay time-constants were comparable for both paradigms and directions of shifts. The optokinetic stimulus had no effect on the bias for either paradigm. CONCLUSIONS: Emerging in both vision-dependent and vision-independent paradigms, the results support the hypothesis that the post-tilt bias results from a shift in the internal estimate of direction of gravity, while optokinetic nystagmus seems not to be a major contributor.