Multi-antigen intranasal vaccine protects against challenge with sarbecoviruses and prevents transmission in hamsters.

Immunization programs against SARS-CoV-2 with commercial intramuscular vaccines prevent disease but are less efficient in preventing infections. Mucosal vaccines can provide improved protection against transmission, ideally for different variants of concern (VOCs) and related sarbecoviruses. Here, we report a multi-antigen, intranasal vaccine, NanoSTING-SN (NanoSTING-Spike-Nucleocapsid), eliminates virus replication in both the lungs and the nostrils upon challenge with the pathogenic SARS-CoV-2 Delta VOC.

An intranasal nanoparticle STING agonist protects against respiratory viruses in animal models.

Respiratory viral infections cause morbidity and mortality worldwide. Despite the success of vaccines, vaccination efficacy is weakened by the rapid emergence of viral variants with immunoevasive properties. The development of an off-the-shelf, effective, and safe therapy against respiratory viral infections is thus desirable.

A competition framework for fixation-preference in strabismus.

Strabismic subjects often develop the ability to fixate on a target with either eye. Previous studies have shown that fixation-preference behavior varies systematically depending on spatial location of the target. We hypothesized that, when an eccentric target is presented, oculomotor fixation-preference in strabismus may be accounted for in a competitive decision framework wherein the brain must choose between two possible retinal errors to prepare a conjugate saccade that results in one of the eyes acquiring the eccentric target.

Human deprivation amblyopia: treatment insights from animal models.

Amblyopia is a common visual impairment that develops during the early years of postnatal life. It emerges as a sequela to eye misalignment, an imbalanced refractive state, or obstruction to form vision. All of these conditions prevent normal vision and derail the typical development of neural connections within the visual system.

Investigation of Selective Innervation of Extraocular Muscle Compartments.

Purpose: Recent magnetic resonance imaging studies have suggested that extraocular muscles (EOM) are further divided into transverse compartments that behave differentially and often unexpectedly during eye movements. Selective innervation of EOM compartments may explain the observation that certain horizontal recti compartments contribute to specific vertical eye movements and that some cyclovertical EOM compartments do not contribute to vertical vergence. We investigated the discharge characteristics of extraocular motoneurons during these eye movement tasks where EOM compartments behaved differentially for evidence of selective innervation.

Unreferenced spatial localization under monocular and dichoptic viewing conditions.

Knowledge of eye position in the brain is critical for localization of objects in space. To investigate the accuracy and precision of eye position feedback in an unreferenced environment, subjects with normal ocular alignment attempted to localize briefly presented targets during monocular and dichoptic viewing. In the task, subjects' used a computer mouse to position a response disk at the remembered location of the target.

Fixation Preference for Visual and Auditory Targets in Monkeys with Strabismus.

Purpose: During binocular viewing, many strabismic subjects choose the eye of fixation depending on the retinotopic location of a visual target. Here, we compare eye choice behavior when orienting to visual and non-visual (auditory) targets.

Methods: Eye movements were measured in two head-fixed exotropic strabismic monkeys in a saccadic task involving either a visual or an auditory stimulus (no visual target information or feedback) during monocular or binocular viewing.

Longitudinal Development of Ocular Misalignment in Nonhuman Primate Models for Strabismus.

Purpose: To investigate the longitudinal change in horizontal and vertical ocular alignment in normal and prism-reared infant monkeys during the critical developmental period.

Methods: Ocular alignment was measured using Hirschberg photographic methods in 6 infant monkeys reared under prism-viewing from day 1 after birth to 4 months, and 2 monkeys reared with normal visual experience. Photographs were acquired twice a week for the first 6 months of life and analyzed to identify pupil center and the first Purkinje image from which eye positions and strabismus angle were calculated.

Response Properties of Cells Within the Rostral Superior Colliculus of Strabismic Monkeys.

Purpose: The superior colliculus (SC) is an important oculomotor structure which, in addition to saccades and smooth-pursuit, has been implicated in vergence. Previously we showed that electrical stimulation of the SC changes strabismus angle in monkey models. The purpose of this study was to record from neurons in the rostral SC (rSC) of two exotropic (XT; divergent strabismus) monkeys (M1, M2) and characterize their response properties, including possible correlation with strabismus angle.

Vertical vergence in nonhuman primates depends on horizontal gaze position.

The goal of this study was to compare vertical fusion capability at different orbital eye positions in normal nonhuman primates and attempt to use this information to isolate the extraocular muscles (EOMs) that mediate vertical vergence. Scleral search coils were used to record movements of both eyes as two normal nonhuman primates (M1, M2) performed a vertical vergence task at different horizontal eye positions. In a control experiment, M1 was also tested at different angles of horizontal vergence.

Neural Plasticity Following Surgical Correction of Strabismus in Monkeys.

Purpose: Although widely practiced, surgical treatment of strabismus has varying levels of success and permanence. In this study we investigated adaptive responses within the brain and the extraocular muscles (EOM) that occur following surgery and therefore determine long-term success of the treatment.

Methods: Single cell responses were collected from cells in the oculomotor and abducens nuclei before and after two monkeys (M1, M2) with exotropia (divergent strabismus) underwent a strabismus correction surgery that involved weakening of the lateral rectus (LR) and strengthening of the medial rectus (MR) muscle of one eye.

Fixational Saccades and Their Relation to Fixation Instability in Strabismic Monkeys.

Purpose: To evaluate the contribution of fixational saccades toward fixation instability in strabismic monkeys.

Methods: Binocular eye movements were measured as six experimental monkeys (five strabismic monkeys and one monkey with downbeat nystagmus) and one normal monkey fixated targets of two shapes (Optotype, Disk) and two sizes (0.5°, 2°) during monocular and binocular viewing.

Strabismus and the Oculomotor System: Insights from Macaque Models.

Disrupting binocular vision in infancy leads to strabismus and oftentimes to a variety of associated visual sensory deficits and oculomotor abnormalities. Investigation of this disorder has been aided by the development of various animal models, each of which has advantages and disadvantages. In comparison to studies of binocular visual responses in cortical structures, investigations of neural oculomotor structures that mediate the misalignment and abnormalities of eye movements have been more recent, and these studies have shown that different brain areas are intimately involved in driving several aspects of the strabismic condition, including horizontal misalignment, dissociated deviations, A and V patterns of strabismus, disconjugate eye movements, nystagmus, and fixation switch.

Comparison of Naso-temporal Asymmetry During Monocular Smooth Pursuit, Optokinetic Nystagmus, and Ocular Following Response in Strabismic Monkeys.

Purpose: Under monocular viewing conditions, humans and monkeys with infantile strabismus exhibit asymmetric naso-temporal (N-T) responses to motion stimuli. The goal of this study was to compare and contrast these N-T asymmetries during 3 visually mediated eye tracking tasks-optokinetic nystagmus (OKN), smooth pursuit (SP) response, and ocular following responses (OFR).

Methods: Two adult strabismic monkeys were tested under monocular viewing conditions during OKN, SP, or OFR stimulation.

Electrical stimulation of superior colliculus affects strabismus angle in monkey models for strabismus.

Disruption of binocular vision during the critical period for development leads to eye misalignment in humans and in monkey models. We have previously suggested that disruption within a vergence circuit could be the neural basis for strabismus. Electrical stimulation in the rostral superior colliculus (rSC) leads to vergence eye movements in normal monkeys.

Longitudinal Evaluation of Eye Misalignment and Eye Movements Following Surgical Correction of Strabismus in Monkeys.

Purpose: Strabismus correction surgery is well documented in both the literature and practice with varying levels of success and permanence. Our goal was to characterize longitudinal changes in eye alignment and eye movements following strabismus correction surgery in a monkey model for developmental strabismus.

Methods: We studied two juvenile rhesus monkeys with exotropia previously induced via an optical prism-rearing paradigm in infancy.

Improvement of Eye Alignment in Adult Strabismic Monkeys by Sustained IGF-1 Treatment.

Purpose: The goal of this study was to determine if continuous application of insulin-like growth factor-1 (IGF-1) could improve eye alignment of adult strabismic nonhuman primates and to assess possible mechanisms of effect.

Methods: A continuous release pellet of IGF-1 was placed on one medial rectus muscle in two adult nonhuman primates (M1, M2) rendered exotropic by the alternating monocular occlusion method during the first months of life. Eye alignment and eye movements were recorded for 3 months, after which M1 was euthanized, and the lateral and medial rectus muscles were removed for morphometric analysis of fiber size, nerve, and neuromuscular density.

Influence of Target Parameters on Fixation Stability in Normal and Strabismic Monkeys.

Purpose: The purpose of this study was to assess the effect of fixation target parameters on fixation instability in strabismic monkeys.

Methods: One normal and three exotropic monkeys were presented with four differently shaped fixation targets, with three diameters, during monocular or binocular viewing. Fixation targets were white on a black background or vice versa.

Motion Information via the Nonfixating Eye Can Drive Optokinetic Nystagmus in Strabismus.

Purpose: Strabismic patients can perceptually suppress information from one eye to avoid double vision. However, evidence from prior studies shows that some parts of the visual field of the deviated eye are not suppressed. Our goal here was to investigate whether motion information available only to the deviated eye can be utilized by the oculomotor system to drive eye movements.

Spatial patterns of fixation-switch behavior in strabismic monkeys.

Purpose: Patients with strabismus perceptually suppress information from one eye to avoid double vision. Mechanisms of visual suppression likely lead to fixation-switch behavior wherein the subject acquires targets with a specific eye depending on target location in space. The purpose of this study was to investigate spatial patterns of fixation-switch behavior in strabismic monkeys.

Muscimol inactivation of caudal fastigial nucleus and posterior interposed nucleus in monkeys with strabismus.

Previously, we showed that neurons in the supraoculomotor area (SOA), known to encode vergence angle in normal monkeys, encode the horizontal eye misalignment in strabismic monkeys. The SOA receives afferent projections from the caudal fastigial nucleus (cFN) and the posterior interposed nucleus (PIN) in the cerebellum. The objectives of the present study were to investigate the potential roles of the cFN and PIN in 1) conjugate eye movements and 2) binocular eye alignment in strabismic monkeys.

Responses of cells in the midbrain near-response area in monkeys with strabismus.

Purpose: To investigate whether neuronal activity within the supraoculomotor area (SOA-monosynaptically connected to medial rectus motoneurons and encode vergence angle) of strabismic monkeys was correlated with the angle of horizontal misalignment and therefore helps to define the state of strabismus.

Methods: Single-cell neural activity was recorded from SOA neurons in two monkeys with exotropia as they performed eye movement tasks during monocular viewing.

Results: Horizontal strabismus angle varied depending on eye of fixation (dissociated horizontal deviation) and the activity of SOA cells (n = 35) varied in correlation with the angle of strabismus.

Conjugate adaptation of smooth pursuit during monocular viewing in strabismic monkeys with exotropia.

Purpose: Humans and monkeys are able to adapt their smooth pursuit output when challenged with consistent errors in foveal/parafoveal image motion during tracking. Visual motion information from the retina is known to be necessary for guiding smooth pursuit adaptation. The purpose of this study is to determine whether retinal motion signals delivered to one eye during smooth pursuit produce adaptation in the fellow eye.