Search Results (44)

Visual behaviour in zebrafish, often measured by the optokinetic reflex (OKR), serves as a valuable model for studying aspects of human neurological and ocular diseases and for conducting therapeutic or toxicology assays. Traditional methods for OKR analysis often rely on binarization techniques (threshold-based conversion of images to black and white) or costly software, which limits their utility in low-contrast settings or hypopigmented disease models. Here, we present a novel deep learning pipeline for OKR analysis, using ResNet-50 within the DeepLabCut framework in a Python Version 3.10 environment. Our approach employs object tracking to enable robust eye movement quantification, regardless of variations in contrast or pigmentation. OKR responses were elicited in both wild-type and slc45a2 (albino) mutant zebrafish larvae at 5 days post-fertilisation, using a mini-LED arena with a rotating visual stimulus. Eye movements were recorded and analysed using both conventional software and our deep learning approach. We demonstrate that the deep learning model achieves comparable accuracy to traditional methods, with the added benefits of applicability in diverse lighting conditions and in hypopigmented larvae. Statistical analyses, including Bland–Altman tests, confirmed the reliability of the deep learning model. While this study focuses on 5-day-old zebrafish larvae under controlled conditions, the pipeline is adaptable across developmental stages, pigmentation types, and behavioural assays. With appropriate adjustments to experimental parameters, it could be applied to broader behavioural studies, including social interactions and predator–prey dynamics in ocular and neurological disease models. Full article

Pupil responses and optokinetic nystagmus (OKN) are known to vary with the brightness and direction of motion of attended stimuli, as well as gaze position. However, whether these processes are controlled by a common mechanism remains unclear. In this study, we investigated how OKN latency relates to pupil response latency under two conditions: gaze shifts (eye movement) and attention shifts (covert attention without eye movement). As a result, while OKN showed consistent temporal changes across both gaze and attention conditions, pupillary responses exhibited distinct patterns. Moreover, the results revealed no significant correlation between pupil latency and OKN latency in either condition. These findings suggest that, although OKN and pupillary responses are influenced by similar attentional processes, their underlying mechanisms may differ. Full article

Background/Objectives: Vestibular Physical Therapy (VPT) plays a crucial role in the rehabilitation of patients with vestibular disorders by promoting vestibular compensation through adaptation, habituation, and substitution mechanisms. While traditional VPT approaches have demonstrated effectiveness in restoring balance and gaze stability, some patients with chronic vestibular dysfunction continue to experience persistent deficits. Methods: review of recent advancements in neuroplasticity research suggest the need for updated rehabilitation strategies that integrate sensorimotor substitution, saccadic training, optokinetic stimulation, and cognitive–motor dual-task training to optimize vestibular compensation. Results: This perspective article explores innovative VPT approaches aimed at improving dynamic gaze and postural stability in a more challenging way. We emphasize the importance of personalized rehabilitation strategies that leverage multisensory integration to enhance neuroplastic recovery. Conclusions: By refining VPT interventions, we can maximize functional outcomes and improve the quality of life for individuals with vestibular disorders. Full article

Retinal models play a pivotal role in translational drug development, bridging preclinical research and therapeutic applications for both ocular and systemic diseases. This review highlights the retina as an ideal organ for studying advanced therapies, thanks to its immune privilege, vascular and neuronal networks, accessibility, and advanced imaging capabilities. Preclinical retinal disease models offer unparalleled insights into inflammation, angiogenesis, fibrosis, and hypoxia, utilizing clinically translatable bioimaging tools like fundoscopy, optical coherence tomography, confocal scanning laser ophthalmoscopy, fluorescein angiography, optokinetic tracking, and electroretinography. These models have driven innovations in anti-inflammatory, anti-angiogenic, and neuroprotective strategies, with broader implications for systemic diseases such as rheumatoid arthritis, Alzheimer’s, and fibrosis-related conditions. By emphasizing the integration of the 3Rs principles and novel imaging modalities, this review highlights how retinal research not only enhances therapeutic precision but also minimizes ethical concerns, paving the way for more predictive and human-relevant approaches in drug development. Full article

Optic neuritis is an inflammatory demyelinating disease of the optic nerve that often occurs in multiple sclerosis (MS) patients. Sixty percent of patients develop some level of permanent visual loss due to retinal ganglion cell (RGC) damage following optic neuritis, with no known treatment to prevent this loss. Prior studies showed that MP201, a prodrug of 2,4-dinitrophenol (DNP) administered in the experimental autoimmune encephalitis (EAE) mouse model of MS attenuated optic neuritis with preserved vision, increased retinal ganglion cell (RGC) survival, decreased axon loss, and reduced demyelination. Oral administration of MP201, which converts to active form DNP after entry in the portal vein, decreases mitochondrial-derived reactive oxygen species (ROS) and restores calcium homeostasis, which are both implicated in many neurodegenerative diseases. Due to the established therapeutic benefits of prodrug MP201 in EAE mice, we hypothesized that administration of DNP itself may also have significant potential for therapeutic effects. Here, effects of varying doses of DNP treatment in EAE mice were assessed by the extent of spinal cord paralysis, optokinetic response (OKR), RGC survival, and optic nerve demyelination and inflammation. Results show that daily oral doses of 5-10 mg/kg DNP initiated after onset of EAE can significantly reduce spinal cord paralysis, a marker of the EAE MS-like disease, by day 42 after disease induction. DNP treatment significantly reduces RGC loss induced by optic neuritis in EAE mice; however, effects of DNP do not significantly improve visual function, or optic nerve demyelination and inflammation. Current studies show DNP treatment promotes increased RGC survival, but continued inflammation and demyelination likely reduce visual function, suggesting future studies examining combination therapy of DNP with anti-inflammatory agents may be warranted. Full article

Background/Objectives: Fabry disease is an X-linked lysosomal storage disease. Earlier studies have mentioned dizziness/balance issues and vestibular involvement as a symptom of Fabry disease. Research on the matter remains scarce. This pilot study aims to show the prevalence of dizziness/balance issues and whether it is due to peripheral, central, or other factors. Methods: A Dizziness Handicap Inventory, with added questions, was sent out to 91 Fabry patients to estimate the prevalence of dizziness/balance issues. Additionally, this study reports analyses from eight Fabry patients with self-reported dizziness/balance issues who were offered referrals for in-depth investigations of their condition. All eight underwent a comprehensive oto-neurological examination, Videonystagmography, a Video Head impulse test, vestibular myogenic evoked potential, and audiometry. Results: A total of 55 of the 91 patients with Fabry disease answered the survey. Of these, 78.2% felt symptoms of dizziness/balance issues. The most common form of dizziness/balance issues was short-lasting attacks. All eight ENT-examined patients had normal outer and middle ear conditions. Five of eight Fabry patients had abnormal results in the optokinetic test and audiometry. Conclusions: The survey showed a high prevalence of dizziness/balance issues in Fabry patients. The abnormal optokinetic test suggested a central cause and was the only objective measurement we found that could lead to an explanation for dizziness/balance issues. Polypharmacy was present in all eight examined patients and could also explain the dizziness/balance issues in Fabry patients. There is no other clear pattern regarding the characteristics of dizziness/balance issues in Fabry patients in this exploratory study. Full article

Background/Objectives: Galvanic vestibular stimulation (GVS) integrated into virtual reality (VR) environments enhances immersion and mitigates cybersickness. It is well known that GVS can affect standing balance. Most studies have investigated the effects of GVS in VR in seated conditions. The purpose of this study was to evaluate the impact of joint GVS and VR with moving visual stimulus on standing balance. Methods: Using a repeated measures counter-balanced design, motion sickness, postural sway, and velocity utilizing the center of pressure (COP) along the mediolateral (ML) and anteroposterior (AP) axes were obtained in 18 subjects during optokinetic (OPK) stimulus (black and white vertical bars moving from left to the right) in VR across three interventions: GVS in the same direction of visual stimulus—left to right ear (Positive GVS), GVS in the opposite direction of visual stimulus—right to left ear (Negative GVS), and without GVS (Null GVS). Motion sickness symptom scoring was obtained using the Pensacola Diagnostic Index. Results: The PDI score was increased significantly in the Negative GVS. The root mean square and sway range of COP along ML was greater during the Positive GVS and Negative GVS than the Null GVS, while, along AP, it was only greater during Negative GVS. During Positive GVS, mean positive and negative peak velocities, only in ML, were increased and decreased, respectively. During Negative GVS, only negative peak velocities in both ML and AP directions were decreased. Conclusions: This research highlights the importance of testing combined VR and GVS to assess standing balance while mitigating cybersickness. Full article

Inherited retinal degenerations (IRDs) are a group of genetic disorders characterized by the progressive degeneration of retinal cells, leading to irreversible vision loss. SLC4A7 has emerged as a candidate gene associated with IRDs, yet its mechanisms remain largely unknown. This study aims to investigate the role of slc4a7 in retinal development and its associated molecular pathogenesis in zebrafish. Morpholino oligonucleotide knockdown, CRISPR/Cas9 genome editing, quantitative RT-PCR, eye morphometric measurements, immunofluorescent staining, TUNEL assays, visual motor responses, optokinetic responses, rescue experiments, and bulk RNA sequencing were used to assess the impact of slc4a7 deficiency on retinal development. Our results demonstrated that the knockdown of slc4a7 resulted in a dose-dependent reduction in eye axial length, ocular area, and eye-to-body-length ratio. The fluorescence observations showed a significant decrease in immunofluorescence signals from photoreceptors and in mCherry fluorescence from RPE in slc4a7-silenced morphants. TUNEL staining uncovered the extensive apoptosis of retinal cells induced by slc4a7 knockdown. Visual behaviors were significantly impaired in the slc4a7-deficient larvae. GO and KEGG pathway analyses reveal that differentially expressed genes are predominantly linked to aspects of vision, ion channels, and phototransduction. This study demonstrates that the loss of slc4a7 in larvae led to profound visual impairments, providing additional insights into the genetic mechanisms predisposing individuals to IRDs caused by SLC4A7 deficiency. Full article

The effects of brain-derived neurotrophic factor (BDNF) on retinal ganglion cell (RGC) survival and visual function were assessed in rat and mouse models of optic nerve (ON) crush. ONs were crushed on Day 1, followed by intravitreal injections of a vehicle or BDNF on Days 1 and 8. The spatial frequency threshold was measured using optokinetic tracking on Days 7 and 14. On Day 15, ganglion cell complex (GCC) thickness was quantified using optical coherence tomography. Furthermore, all eyes were enucleated for immunohistochemical analysis of the surviving RGC somas and axons. BDNF significantly reduced the RGC soma in mice and increased GCC thickness in intact eyes, with apparent axonal swelling in both species. It displayed significantly greater RGC soma survival in eyes with ON injury, with moderately thicker axonal bundles in both species and a thicker GCC in rats. Visual function was significantly reduced in all ON-crushed animals, regardless of BDNF treatment. Thus, we obtained a comprehensive analysis of the structural and functional impact of BDNF in intact and ON-crushed eyes in two rodent models. Our results provide a foundation for further BDNF evaluation and the design of preclinical studies on neuroprotectants using BDNF as a reference positive control. Full article

Background: The aim of the study was to demonstrate the influence of virtual reality (VR) exposure on postural stability and determine the mechanism of this influence. Methods: Twenty-six male participants aged 21–23 years were included, who underwent postural stability assessment twice before and after a few minute of single VR exposure. The VR projection was a computer-generated simulation of the surrounding scenery. Postural stability was assessed using the Sensory Organization Test (SOT), using Computerized Dynamic Posturography (CDP). Results: The findings indicated that VR exposure affects the visual and vestibular systems. Significant differences (p < 0.05) in results before and after VR exposure were observed in tests on an unstable surface. It was confirmed that VR exposure has a positive influence on postural stability, attributed to an increase in the sensory weight of the vestibular system. Partial evidence suggested that the reduction in vestibulo-ocular reflex (VOR) reinforcement may result in an adaptive shift to the optokinetic reflex (OKR). Conclusions: By modifying the process of environmental perception through artificial sensory simulation, the influence of VR on postural stability has been demonstrated. The validity of this type of research is determined by the effectiveness of VR techniques in the field of vestibular rehabilitation. Full article

Purpose: Resveratrol is a natural polyphenol which has a very low bioavailability but whose antioxidant, anti-inflammatory and anti-apoptotic properties may have therapeutic potential for the treatment of neurodegenerative diseases such as multiple sclerosis (MS). Previously, we reported the oral administration of resveratrol nanoparticles (RNs) elicited a neuroprotective effect in an experimental autoimmune encephalomyelitis (EAE) mouse model of MS, at significantly lower doses than unconjugated resveratrol (RSV) due to enhanced bioavailability. Furthermore, we demonstrated that the intranasal administration of a cell-derived secretome-based therapy at low concentrations leads to the selective neuroprotection of the optic nerve in EAE mice. The current study sought to assess the potential selective efficacy of lower concentrations of intranasal RNs for attenuating optic nerve damage in EAE mice. Methods: EAE mice received either a daily intranasal vehicle, RNs or unconjugated resveratrol (RSV) for a period of thirty days beginning on the day of EAE induction. Mice were assessed daily for limb paralysis and weekly for visual function using the optokinetic response (OKR) by observers masked to treatment regimes. After sacrifice at day 30, spinal cords and optic nerves were stained to assess inflammation and demyelination, and retinas were immunostained to quantify retinal ganglion cell (RGC) survival. Results: Intranasal RNs significantly increased RGC survival at half the dose previously shown to be required when given orally, reducing the risk of systemic side effects associated with prolonged use. Both intranasal RSV and RN therapies enhanced RGC survival trends, however, only the effects of intranasal RNs were significant. RGC loss was prevented even in the presence of inflammatory and demyelinating changes induced by EAE in optic nerves. Conclusions: The intranasal administration of RNs is able to reduce RGC loss independent of the inflammatory and demyelinating effects on the optic nerve and the spinal cord. The concentration of RNs needed to achieve neuroprotection is lower than previously demonstrated with oral administration, suggesting intranasal drug delivery combined with nanoparticle conjugation warrants further exploration as a potential neuroprotective strategy for the treatment of optic neuritis, alone as well as in combination with glucocorticoids. Full article

Adults with obesity experience high rates of disability and rapid functional decline. Identifying movement dysfunction early can direct intervention and disrupt disability development; however, subtle changes in movement are difficult to detect with the naked eye. This study evaluated how a portable, inertial measurement unit (IMU)-based motion capture system compares to a laboratory-based optokinetic motion capture (OMC) system for evaluating gait kinematics in adults with obesity. Ten adults with obesity performed overground walking while equipped with the OMC and IMU systems. Fifteen gait cycles for each participant were extracted for the 150 total cycles analyzed. Kinematics were compared between OMC and IMU across the gait cycles (coefficient of multiple correlations), at clinically significant time points (interclass correlations), and over clinically relevant ranges (Bland–Altman plots). Sagittal plane kinematics were most similar between systems, especially at the knee. Sagittal plane joint angles at clinically meaningful timepoints were poorly associated except for ankle dorsiflexion at heel strike (ρ = 0.38) and minimum angle (ρ = 0.83). All motions except for ankle dorsiflexion and hip abduction had >5° difference between systems across the range of angles measured. While IMU-based motion capture shows promise for detecting subtle gait changes in adults with obesity, more work is needed before this method can replace traditional OMC. Future work should explore standardization procedures to improve consistency of IMU motion capture performance. Full article

Optokinetic reflex (OKR) assays in zebrafish models are a valuable tool for studying a diverse range of ophthalmological and neurological conditions. Despite its increasing popularity in recent years, there are no clear reporting guidelines for the assay. Following reporting guidelines in research enhances reproducibility, reduces bias, and mitigates underreporting and poor methodologies in published works. To better understand optimal reporting standards for an OKR assay in zebrafish, we performed a systematic literature review exploring the animal, environmental, and technical factors that should be considered. Using search criteria from three online databases, a total of 109 research papers were selected for review. Multiple crucial factors were identified, including larval characteristics, sample size, fixing method, OKR set-up, distance of stimulus, detailed stimulus parameters, eye recording, and eye movement analysis. The outcome of the literature analysis highlighted the insufficient information provided in past research papers and the lack of a systematic way to present the parameters related to each of the experimental factors. To circumvent any future errors and champion robust transparent research, we have created the zebrafish optokinetic (ZOK) reflex minimal reporting guideline. Full article

As animals execute essential behaviors like foraging, they must orient with respect to the space around them, requiring some neural/behavioral mechanism for spatial navigation. One such navigation mechanism is path integration, whereby animals recall their starting point by creating a memory-stored home vector. In some animals, this is stored in an egocentric frame of reference; however, it remains unclear what comprises this in animals’ spatial memory. The fiddler crab Uca pugilator makes an excellent model to investigate the nature of the egocentric frame of reference because they appear to path integrate using self-motion cues to form an egocentric vector. We hypothesized that the home vector direction is governed by the optokinetic system, since the eye–body angle explicitly reflects the deviation of the body axis from home direction as optokinetic eye movements stabilize the eyes against body rotation. To test this hypothesis, we monitored eye and body movements during foraging excursions of crabs showing varying degrees of visual stabilization. We found that crabs with good eye stability had more accurate home vectors than those with poor eye stability, and the quantitative degree of stability accurately predicted the crabs’ perception of home direction. These results suggest that eye movement reflexes may establish the homing direction in path integrating fiddler crabs. Full article

Background: Vestibular migraine (VM) is the most frequent etiology of recurrent spontaneous episodic vertigo. Vestibular and oculomotor abnormalities have been described in VM; however, the diagnosis is currently based on symptoms. The objective of this study was to determine the most frequent abnormalities in videonystagmography (VNG), caloric testing (Cal) and video head impulse test (vHIT) in patients with VM. Methods: A retrospective cohort study was conducted, including all VM and probable VM patients seen from January 2021 to July 2022. Demographics, auditory symptoms and results via VNG, Cal and vHIT were evaluated. VNG results were compared with a control group. Results: Sixty patients, 81.7% with VM and 18.3% with probable vestibular migraine, were included. VNG revealed the following abnormalities: 21.7% spontaneous nystagmus; 33.3% positional nystagmus, mostly central; 26.7% optokinetic nystagmus; 56.7% smooth pursuit abnormalities and 70% saccade test abnormalities, mostly velocity and latency. An abnormal unilateral caloric response was seen in 22.9%, while vHIT revealed a low gain in at least one canal in 21.7%, and saccades were seen in at least one canal with normal gains in 18.3%. Concordant results between Cal and lateral vHIT were seen in 77.1% of cases. Conclusions: Although VM is a clinical diagnosis, vestibular and oculomotor abnormalities are commonly seen. The most frequent oculomotor findings were an abnormal saccade test, abnormal smooth pursuit and central positional nystagmus. Full article