Search Results (11)

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

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

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

Optic neuritis (ON), the most common ocular manifestation of multiple sclerosis, is an autoimmune inflammatory demyelinating disease also characterized by degeneration of retinal ganglion cells (RGCs) and their axons, which commonly leads to visual impairment despite attempted treatments. Although ON disease etiology is not known, changes in the redox system and exacerbated optic nerve inflammation play a major role in the pathogenesis of the disease. Silent information regulator 1 (sirtuin-1/SIRT1) is a ubiquitously expressed NAD⁺-dependent deacetylase, which functions to reduce/prevent both oxidative stress and inflammation in various tissues. Non-specific upregulation of SIRT1 by pharmacologic and genetic approaches attenuates RGC loss in experimental ON. Herein, we hypothesized that targeted expression of SIRT1 selectively in RGCs using an adeno-associated virus (AAV) vector as a delivery vehicle is an effective approach to reducing neurodegeneration and preserving vision in ON. We tested this hypothesis through intravitreal injection of AAV7m8.SNCG.SIRT1, an AAV2-derived vector optimized for highly efficient SIRT1 transgene transfer and protein expression into RGCs in mice with experimental autoimmune encephalomyelitis (EAE), a model of multiple sclerosis that recapitulates optic neuritis RGC loss and axon demyelination. Our data show that EAE mice injected with a control vehicle exhibit progressive alteration of visual function reflected by decreasing optokinetic response (OKR) scores, whereas comparatively, AAV7m8.SNCG.SIRT1-injected EAE mice maintain higher OKR scores, suggesting that SIRT1 reduces the visual deficit imparted by EAE. Consistent with this, RGC survival determined by immunolabeling is increased and axon demyelination is decreased in the AAV7m8.SNCG.SIRT1 RGC-injected group of EAE mice compared to the mouse EAE counterpart injected with a vehicle or with control vector AAV7m8.SNCG.eGFP. However, immune cell infiltration of the optic nerve is not significantly different among all EAE groups of mice injected with either vehicle or AAV7m8.SNCG.SIRT1. We conclude that despite minimally affecting the inflammatory response in the optic nerve, AAV7m8-mediated SIRT1 transfer into RGCs has a neuroprotective potential against RGC loss, axon demyelination and vison deficits associated with EAE. Together, these data suggest that SIRT1 exerts direct effects on RGC survival and function. Full article

Background: Gene therapy is a therapeutic possibility for retinitis pigmentosa (RP), in which therapeutic transgenes are currently delivered to the retina by adeno-associated viral vectors (AAVs). Although their safety and efficacy have been demonstrated in both clinical and preclinical settings, AAVs present some technical handicaps, such as limited cargo capacity and possible immunogenicity in repetitive doses. The development of alternative, non-viral delivery platforms like nanoparticles is of great interest to extend the application of gene therapy for RP. Methods: Amino-functionalized mesoporous silica-based nanoparticles (N-MSiNPs) were synthesized, physico-chemically characterized, and evaluated as gene delivery systems for human cells in vitro and for retinal cells in vivo. Transgene expression was evaluated by WB and immunofluorescence. The safety evaluation of mice subjected to subretinal injection was assessed by ophthalmological tests (electroretinogram, funduscopy, tomography, and optokinetic test). Results: N-MSiNPs delivered transgenes to human cells in vitro and to retinal cells in vivo. No adverse effects were detected for the integrity of the retinal tissue or the visual function of treated eyes. N-MSiNPs were able to deliver a therapeutic transgene candidate for RP, PRPF31, both in vitro and in vivo. Conclusions: N-MSiNPs are safe for retinal delivery and thus a potential alternative to viral vectors. Full article

Thyroid hormones (THs; T3 and T4) enter cells using specific transporters and regulate development and metabolism. Mutation in the TH transporter monocarboxylate transporter 8 (MCT8, SLC16A2) is associated with brain hypothyroidism and neurological impairment. We established mct8 mutant (mct8−/−) zebrafish as a model for MCT8 deficiency, which causes endocrinological, neurological, and behavioral alterations. Here, we profiled the transcriptome of mct8−/− larvae. Among hundreds of differentially expressed genes, the expression of a cluster of vision-related genes was distinct. Specifically, the expression of the opsin 1 medium wave sensitive 2 (opn1mw2) decreased in two mct8 mutants: mct8−/− and mct8^−25bp−/− larvae, and under pharmacological inhibition of TH production. Optokinetic reflex (OKR) assays showed a reduction in the number of conjugated eye movements, and live imaging of genetically encoded Ca²⁺ indicator revealed altered neuronal activity in the pretectum area of mct8^−25bp−/− larvae. These results imply that MCT8 and THs regulate the development of the visual system and suggest a mechanism to the deficiencies observed in the visual system of MCT8-deficiency patients. Full article

Traumatic brain injury (TBI) results in a number of impairments, often including visual symptoms. In some cases, visual impairments after head trauma are mediated by traumatic injury to the optic nerve, termed traumatic optic neuropathy (TON), which has few effective options for treatment. Using a murine closed-head weight-drop model of head trauma, we previously reported in adult mice that there is relatively selective injury to the optic tract and thalamic/brainstem projections of the visual system. In the current study, we performed blunt head trauma on adolescent C57BL/6 mice and investigated visual impairment in the primary visual system, now including the retina and using behavioral and histologic methods at new time points. After injury, mice displayed evidence of decreased optomotor responses illustrated by decreased optokinetic nystagmus. There did not appear to be a significant change in circadian locomotor behavior patterns, although there was an overall decrease in locomotor behavior in mice with head injury. There was evidence of axonal degeneration of optic nerve fibers with associated retinal ganglion cell death. There was also evidence of astrogliosis and microgliosis in major central targets of optic nerve projections. Further, there was elevated expression of endoplasmic reticulum (ER) stress markers in retinas of injured mice. Visual impairment, histologic markers of gliosis and neurodegeneration, and elevated ER stress marker expression persisted for at least 30 days after injury. The current results extend our previous findings in adult mice into adolescent mice, provide direct evidence of retinal ganglion cell injury after head trauma and suggest that axonal degeneration is associated with elevated ER stress in this model of TON. Full article

Optokinetic nystagmus (OKN) is an involuntary eye movement induced by motion of a large proportion of the visual field. It consists of a “slow phase (SP)” with eye movements in the same direction as the movement of the pattern and a “fast phase (FP)” with saccadic eye movements in the opposite direction. Study of OKN can reveal valuable information in ophthalmology, neurology and psychology. However, the current commercially available high-resolution and research-grade eye tracker is usually expensive. Methods & Results: We developed a novel fast and effective system combined with a low-cost eye tracking device to accurately quantitatively measure OKN eye movement. Conclusions: The experimental results indicate that the proposed method achieves fast and promising results in comparisons with several traditional approaches. Full article

Looking at the future path and/or the tangent point (TP) have been identified as car drivers’ gaze targets in many studies on curve driving. Yet little is known in detail about these "fixations to the road". We quantitatively analyse gaze behavior at the level of individual fixations in real on-road data. We find that while gaze tracks the TP area, this pattern consists of fast optokinetic movements (smooth pursuit and fast resetting saccadic movements). Gaze is not “fixed” to the TP. We also relate eye-movements to a reference direction fixed to a point on the trajectory of the vehicle (curve exit), showing that fixations lose their pursuit-like character in this rotating system. The findings are discussed in terms of steering models and neural levels of oculomotor control. Full article