Scaling Properties of Optokinetic Nystagmus Amplitude Sequence

Optokinetic nystagmus (OKN) is rhythmic eye movements, back and forth, with a slow and fast phase when the eyes are presented for full-field visual stimulus. OKN was recorded in a healthy subject for four conditions, stripes moving 30°/s left and right and 60°/s left and right. In this paper, surrogate data analysis was applied to test the Hurst exponents for increasing time horizons for the integrated OKN amplitude sequences statistically against 100 shuffled sequences (i.e., the serial dependency of the original data sequences is broken by changing the order of the sequence). The result shows that the pattern of the OKN amplitude sequence scales statistically different (p < 0.01) compared to random permutations of the same numbers for scaling shorter than 16 nystagmus components (slow and fast phases) for all four test conditions.

Evaluation of Driver Distraction with Changes in Gaze Direction Based on a Vestibulo-Ocular Reflex Model

With the aim of improving parameter identification and, eventually, evaluating driver distraction with changes in gaze direction, we applied a genetic algorithm (GA) method to identify parameters for an existing vestibulo-ocular reflex (VOR) model. By changing the initial inputs to the GA and fixing two parameters pertaining to the horizontal direction, we achieved improved parameter identification with a lower mean-square error. The influence of driver distraction on eye movement with changes in gaze direction was evaluated from the difference between the predicted and observed VOR in the vertical axis. When a driver was given an additional mental workload, the mean-square error between the measured and simulated values was bigger than that in the absence of the mental workload. This confirmed the relationship between driver distraction and eye movement in the vertical direction. We hope that this method can be applied in evaluating driver distraction.

AB027.Nogo-A neutralisation improves vision recovery after retinal injury

Background:In glaucoma and after an ischemic injury of the retina,excessive activation of N-Methyl-D-Aspartate receptors,a type of glutamatergic receptors,induces the death of retinal ganglion cells and an irreversible vision loss.The painless loss of retinal cells does not allow for a swift diagnostic and treatment of retinal damages.There is no efficient therapy to improve retinal functions in this case.In order to develop new therapeutic approaches for retinal injury,we propose,in this study,to stimulate neuronal plasticity of the visual system by neutralising the glial protein,Nogo-A.The inhibitory action of this protein on axonal regeneration is well known in spinal cord injuries but not in the visual system.We thus studied the function of Nogo-A in vision recovery in mice.Methods:Nogo-A activities were chronically blocked by deleting its gene in KO mice and acutely,by intravitreal injections of an antibody known as 11C7.Inner retina lesions were done by injection of 0.5 or 5 nmol of NMDA in the vitreous humor.A PBS buffer was administered in control animals.The visual system functions were accessed with an optokinetic test in awake mice,by electroretinography(ERG)in the eye and visual evoked potentials in the visual cortex.Cell survival of retinal ganglion cells,amacrine and bipolar cells was evaluated on histological sections by immunofluorescence.Changes in expression of Nogo-A,its receptors and neuronal plasticity associated molecules were observed by Western blot and q-PCR.Results:At NMDA doses of≤0.5 nmol,Nogo-A KO mice show a recovery of optokinetic responses much faster than in WT mice.Surprisingly,a single injection of the antibody,11C7 was sufficient to improve VEPs of NMDA injured animals as compared to control antibody.Furthermore,ERGs showed that a dose of 0.5 nmol induced retinal lesions limited to the ganglion cell layer,with significant changes to the VEPs but without influencing photoreceptors and inner nuclear layer cells functions.However,5 nmol of NMDA affected the survival of inner nuclear layer cells and reduced by~50%their activity.Conclusions:Our results show that the neutralisation of Nogo-A can improve visual functions after injury to the inner retina.Inhibition of Nogo-A could thus be an efficient way to treat pathologies like glaucoma.

AB028.Mesenchymal stem cells repair retinal vascular damage in retinopathy of prematurity mouse model

Background:Retinopathy of prematurity is a leading cause of visual impairment and blindness in infants.Exposure of premature babies to the hyperoxic extrauterine environment leads to vaso-obliteration(VO),followed by ischemia,and subsequently pathological intravitreal neovascularization(NV)in the immature retina.Current treatments target only aberrant intravitreal vessel growth without repopulating the avascular regions of the retina.Thus,there is a dire need of new therapies that arrest pathological NV and promote normal retinal revascularization.Mesenchymal stem cells(MSCs)have shown the ability to migrate to the damaged tissue in different animal models and enhance vascularization.We,therefore,investigated whether MSCs can promote vascular repair in a mouse model of ROP.Methods:Oxygen-induced retinopathy(OIR)model was used herein.Postnatal day 7(P7)mice were subjected to 75%O2 until P12 to induce VO followed by 5 days of room air leading to NV.Compact bone-derived MSCs were isolated from adult C57BL/6 mice and cultured either in hypoxia(5%O2)or normoxia(21%O2).Conditioned media(CM)was collected 24 hours later and injected intravitreally in P12 OIR retinas to assess vascular repair.To determine possible factors involved in MSC-induced revascularization,gene expression analysis was performed on P17 OIR retinas.In vitro,we investigated the effect of MSC-CM on microglial polarization using quantitative PCR and flow cytometry.Results:Hypoxic MSC-CM significantly(P<0.01)decreased both VO and NV areas in comparison to the normoxic counterpart.Levels of IGF-1 and VEGF were significantly high in MSC-injected OIR retinas.Moreover,gene expression levels of pro-inflammatory cytokines(IL-1β,TNFα)dropped whereas levels of anti-inflammatory cytokines(IL-10,IL-4)increased.Treatment of pro-inflammatory M1 microglia with MSC-CM decreased the gene expression of IL-1βand TNFα,and iNOS(M1 marker)at the transcript and protein levels.Conclusions:In this study,we demonstrated that MSCs promote healthy vessel growth in OIR retinas via a paracrine fashion by regulating expression of angiogenic factors and modulating inflammation.

Gamma-aminobutyric acid and GABA_A receptors are involved in directional selectivity of pretectal neurons in pigeons

The present study describes the effects of gamma-aminobutyric acid (GABA) and its antagonists, bicuculline and 2-hydroxysaclofen, on visual responses of neurons in the pigeon nucleus lentiformis mesencephali (nLM). The results indicate that GABA significantly reduces both spontaneous activity and visual responsiveness, and GABAA antagonist bicuculline but not GABAB antagonist 2-hydroxysaclofen enhances visual responses of nLM cells examined. Furthermore, inhibition produced by motion in the null-direction of pretectal neurons is diminished by bicuculline but not by 2-hydroxysaclofen. It is therefore concluded that the null-direction inhibition of directional cells in the pigeon nLM is predominantly mediated by GABA and GABAA receptors. This inhibition may at least in part underlie directional asymmetry of optokinetic responses.