Electroretinography Measurements Research Articles

RETINAL AGING IN COMPANION DOGS

Abstract Companion dogs cohabit with humans in approximately 45% of US households. They experience similar environmental exposures and lifestyles to their human companions, and have shown sensory, cognitive, and neurological decline with aging. The relationship between age and retinal neurologic function in dogs has not been described. The aim of this study was to determine associations between age and retinal full-field electroretinographic measures in companion dogs, an important translational model species for human neurologic aging. Healthy adult companion dogs with no ophthalmic abnormalities were included (n=54, 18 male, 36 female, median weight 25.7kg, median age 89 months). Unilateral full-field light-adapted and dark-adapted electroretinography (ERG) was performed using a handheld device, with mydriasis and topical anesthesia. Standard least squares effect leverage models were used with log transformed data to determine the cross-sectional effect of age, sex, and bodyweight on ERG amplitudes and peak times. Age and sex were significantly associated with ERG outcome variables, more consistently with ERG amplitude than peak time; age had the largest and most significant effect leverage on outcomes (significantly affecting 3/9 peak time and 8/10 amplitude outcome variables). Younger and female dogs had higher ERG amplitudes. Body weight had no significant effect on any outcome. Our finding that aged companion dogs have reduced ERG amplitudes and prolonged peak times mirror ERG findings in aging humans. Because dogs have a shorter lifespan compared with humans, they may act as a sentinel species to monitor for emerging risk factors for age-related neurologic decline.

Synergism of mechanisms underlying early-stage changes in retina function in male hyperglycemic db/db mice in the absence and presence of chemically-induced dyslipidemia

The study was designed to quantify retina function in a spontaneous mutation mouse model of diabetes, in which sustained dyslipidemia was induced chemically. The goal of the study was to identify if dyslipidemia in the presence of hyperglycemia resulted in either a synergistic, or a merely additive, exacerbation of retinal and visual dysfunctions in diabetes. Two cohorts of mice, male C57BL/6 and C57BL/KsJ-db/db mice were divided into two groups each. One group of each strain received the triblock copolymer, poloxamer 407 (P-407), administered by intraperitoneal injection (“WT P-407” and “db/db P-407” groups) with saline as a control in the remaining two groups (“WT” and “db/db” groups). Blood glucose, total cholesterol (TC) and total triglyceride (TG) levels were quantified using enzyme-based colorimetric assays. Retina function was measured using electroretinography (ERG) and visual acuity was determined by behaviorally assessing parameters of the optomotor reflex. TC and TG levels were normal in both saline controls (WT) and db/db mice but were significantly elevated in the WT P-407 group (p < 0.01 for TC; p < 0.001 for TG), while levels of the same lipids were further elevated in the db/db P-407 group when compared to the WT P-407 group levels (p < 0.001 for both TC and TG). Behavioral assessment of the optomotor reflex indicated reduced visual acuity for the db/db P-407 group when compared to either the WT P-407 or the db/db groups (p < 0.001, p < 0.0001). ERG measurements of scotopic retina function showed a significant decline in the scotopic b-wave amplitude of the WT P-407 animals (p < 0.01) and a further reduction for the db/db P-407 group when compared to controls (p < 0.0001). Very significant, strong correlations between scotopic b-wave amplitude and implicit time to TC (r = − 0.8376, p = < 0.0001 and r = 0.7069, p = 0.0022, respectively) and TG levels (r = − 0.8554, p = < 0.0001 and r = 0.7150, p = 0.0019, respectively) were found. Dyslipidemia in the presence of hyperglycemia synergistically exacerbated the severity of retinal dysfunction in diabetes. P-407 administration significantly elevated plasma TC and TG levels in male wild-type (WT) and diabetic mice (db/db), but the resulting hyperlipidemia was more significantly pronounced in the diabetic mice. While elevated plasma lipid and blood glucose levels were individually correlated with a decline in retinal function, the combination of both exacerbated retinal dysfunction. This model of combined hyperglycemia and dyslipidemia can be used to dissect individual contributions of features of the metabolic syndrome to the pathogenesis of retinal dysfunction in diabetes.

Rapid RGR-dependent visual pigment recycling is mediated by the RPE and specialized Müller glia

In daylight, demand for visual chromophore (11-cis-retinal) exceeds supply by the classical visual cycle. This shortfall is compensated, in part, by the retinal G-protein-coupled receptor (RGR) photoisomerase, which is expressed in both the retinal pigment epithelium (RPE) and in Müller cells. The relative contributions of these two cellular pools of RGR to the maintenance of photoreceptor light responses are not known. Here, we use a cell-specific gene reactivation approach to elucidate the kinetics of RGR-mediated recovery of photoreceptor responses following light exposure. Electroretinographic measurements in mice with RGR expression limited to either cell type reveal that the RPE and a specialized subset of Müller glia contribute both to scotopic and photopic function. We demonstrate that 11-cis-retinal formed through photoisomerization is rapidly hydrolyzed, consistent with its role in a rapid visual pigment regeneration process. Our study shows that RGR provides a pan-retinal sink for all-trans-retinal released under sustained light conditions and supports rapid chromophore regeneration through the photic visual cycle.

Age-associated changes in electroretinography measures in companion dogs.

To determine the association between age and retinal full-field electroretinographic (ERG) measures in companion (pet) dogs, an important translational model species for human neurologic aging. Healthy adult dogs with no significant ophthalmic abnormalities were included. Unilateral full-field light- and dark-adapted electroretinography was performed using a handheld device, with mydriasis and topical anaesthesia. Partial least squares effect screening analysis was performed to determine the effect of age, sex, body weight and use of anxiolytic medication on log-transformed ERG peak times and amplitudes; age and anxiolytic usage had significant effects on multiple ERG outcomes. Mixed model analysis was performed on data from dogs not receiving anxiolytic medications. In dogs not receiving anxiolytics, median age was 118months (interquartile range 72-140months, n = 77, 44 purebred, 33 mixed breed dogs). Age was significantly associated with prolonged peak times of a-waves (dark-adapted 3 and 10cds/m2 flash p < 0.0001) and b-waves (cone flicker p = 0.03, dark-adapted 0.01cds/m2 flash p = 0.001). Age was also significantly associated with reduced amplitudes of a-waves (dark-adapted 3cds/m2 flash p < 0.0001, 10cds/m2 flash p = 0.005) and b-waves (light-adapted 3cds/m2 flash p < 0.0001, dark-adapted 0.01cds/m2 flash p = 0.0004, 3cds/m2 flash p < 0.0001, 10cds/m2 flash p = 0.007) and flicker (light-adapted 30Hz 3cds/m2 p = 0.0004). Within the Golden Retriever breed, these trends were matched in a cross-sectional analysis of 6 individuals that received no anxiolytic medication. Aged companion dogs have slower and reduced amplitude responses in both rod- and cone-mediated ERG. Consideration of anxiolytic medication use should be made when conducting ERG studies in dogs.

Improvement of retinal function in Alzheimer disease-associated retinopathy by dietary lysophosphatidylcholine-EPA/DHA

Alzheimer disease (AD) is the most prevalent cause of dementia in the elderly. Although impaired cognition and memory are the most prominent features of AD, abnormalities in visual functions often precede them, and are increasingly being used as diagnostic and prognostic markers for the disease. Retina contains the highest concentration of the essential fatty acid docosahexaenoic acid (DHA) in the body, and its deficiency is associated with several retinal diseases including diabetic retinopathy and age related macular degeneration. In this study, we tested the hypothesis that enriching retinal DHA through a novel dietary approach could ameliorate symptoms of retinopathy in 5XFAD mice, a widely employed model of AD. The results show that 5XFAD mice have significantly lower retinal DHA compared to their wild type littermates, and feeding the lysophosphatidylcholine (LPC) form of DHA and eicosapentaenoic acid (EPA) rapidly normalizes the DHA levels, and increases retinal EPA by several-fold. On the other hand, feeding similar amounts of DHA and EPA in the form of triacylglycerol had only modest effects on retinal DHA and EPA. Electroretinography measurements after 2 months of feeding the experimental diets showed a significant improvement in a-wave and b-wave functions by the LPC-diet, whereas the TAG-diet had only a modest benefit. Retinal amyloid β levels were decreased by about 50% by the LPC-DHA/EPA diet, and by about 17% with the TAG-DHA/EPA diet. These results show that enriching retinal DHA and EPA through dietary LPC could potentially improve visual abnormalities associated with AD.

Overexpression of Neuregulin-1 Type III Has Impact on Visual Function in Mice.

Schizophrenia is associated with several brain deficits, including abnormalities in visual processes. Neuregulin-1 (Nrg1) is a family of trophic factors containing an epidermal growth factor (EGF)-like domain. It is thought to play a role in neural development and has been linked to neuropsychiatric disorders. Abnormal Nrg1 expression has been observed in schizophrenia in clinical studies. Moreover, in schizophrenia, there is more and more evidence found about pathological changes of the retina regarding structural, neurochemical and physiological parameters. However, mechanisms of these changes are not well known. To investigate this, we analysed the function of the visual system using electroretinography (ERG) and the measurement of visual evoked potentials (VEP) in transgenic mice overexpressing Nrg1 type III of three different ages (12 weeks, 24 weeks and 55 weeks). ERG amplitudes tended to be higher in transgenic mice than in control mice in 12-week old mice, whereas the amplitudes were almost similar in older mice. VEP amplitudes were larger in transgenic mice at all ages, with significant differences at 12 and 55 weeks (p values between 0.003 and 0.036). Latencies in ERG and VEP measurements did not differ considerably between control mice and transgenic mice at any age. Our data show for the first time that overexpression of Nrg1 type III changed visual function in transgenic mice. Overall, this investigation of visual function in transgenic mice may be helpful to understand corresponding changes that occur in schizophrenia, as they may find use as biomarkers for psychiatric disorders as well as a potential tool for diagnosis in psychiatry.

Evidence for UV-green dichromacy in the basal hymenopteran Sirex noctilio (Siricidae)

A precondition for colour vision is the presence of at least two spectral types of photoreceptors in the eye. The order Hymenoptera is traditionally divided into the Apocrita (ants, bees, wasps) and the Symphyta (sawflies, woodwasps, horntails). Most apocritan species possess three different photoreceptor types. In contrast, physiological studies in the Symphyta have reported one to four photoreceptor types. To better understand the evolution of photoreceptor diversity in the Hymenoptera, we studied the Symphyta Sirex noctilio, which belongs to the superfamily Siricoidea, a closely related group of the Apocrita suborder. Our aim was to (i) identify the photoreceptor types of the compound eye by electroretinography (ERG), (ii) characterise the visual opsin genes of S. noctilio by genomic comparisons and phylogenetic analyses and (iii) analyse opsin mRNA expression. ERG measurements revealed two photoreceptor types in the compound eye, maximally sensitive to 527 and 364 nm. In addition, we identified three opsins in the genome, homologous to the hymenopteran green or long-wavelength sensitive (LW) LW1, LW2 and ultra-violet sensitive (UV) opsin genes. The LW1 and UV opsins were found to be expressed in the compound eyes, and LW2 and UV opsins in the ocelli. The lack of a blue or short-wavelength sensitive (SW) homologous opsin gene and a corresponding receptor suggests that S. noctilio is a UV-green dichromate.

Visual dysfunction in a mouse model of chemotherapy-related neurotoxicity.

e24059 Background: Chemotherapy-related neurotoxicity (CRNT) poses challenges to long-term outcomes of cancer survivors. Visual function remains relatively unexplored in CRNT. Preliminary clinical work from our group suggests contrast sensitivity may be impaired in patients receiving chemotherapy. Here, we sought to isolate effects of chemotherapy on visual dysfunction in a mouse model. Methods: 10-week old C57BL/6J mice received either 4, 7, or 10 weekly intraperitoneal injections of chemotherapy (CTX group; n=15) or physiologic saline (SAL group; n=12). CTX mice received cyclophosphamide (50 mg/kg) and doxorubicin (2 mg/kg). Contrast sensitivity was assessed using an optomotor response (OMR) chamber. Psychometric functions were fitted to OMR contrast response functions to derive measures of contrast sensitivity (K), stimulus responsivity (Rmax), and stimulus selectivity (n). Electroretinography (ERG) waveforms, which measure light-evoked retinal neural activity, were recorded under scotopic (rod-driven) conditions and decomposed to isolate photoreceptor (a-wave), bipolar cell (b-wave), and interneuron amacrine cell (oscillatory potentials [OP]) activity. OMR and ERG were measured prior to and following treatment. Dependent- and independent-sample t-tests assessed within- and between-group changes, respectively, in outcome measures. Results: Outcome measures are reported in Table 1. SAL relative to CTX mice showed greater weight gain (p=0.004). OMR revealed increases in Rmax (pCTX=0.002; pSAL=0.11) and K (pCTX=0.80; pSAL=0.06) parameters in SAL but not CTX mice. ERG results revealed significant declines in OP peak frequency in CTX relative to SAL mice (p=0.006). Other OMR and ERG measures showed no within- or between-group differences (p&gt;0.10). Decreases in weight were associated with decreases in Rmax (R2=0.25, p=.008) and OP peak frequency (R2=0.20, p=.02). Conclusions: Our animal model showed chemotherapy-related visual dysfunction. Mice receiving chemotherapy showed relative declines in contrast sensitivity, stimulus responsivity, and oscillatory neural activity, suggestive of disrupted neuronal circuits within the visual pathway. Future studies will focus on understanding neuronal mechanisms of visual pathway dysfunction and translating findings to clinical studies. [Table: see text]

Retinal bioavailability and functional effects of a synthetic very-long-chain polyunsaturated fatty acid in mice

Rare, nondietary very-long-chain polyunsaturated fatty acids (VLC-PUFAs) are uniquely found in the retina and a few other vertebrate tissues. These special fatty acids play a clinically significant role in retinal degeneration and development, but their physiological and interventional research has been hampered because pure VLC-PUFAs are scarce. We hypothesize that if Stargardt-3 or age-related macular degeneration patients were to consume an adequate amount of VLC-PUFAs that could be directly used in the retina, it may be possible to bypass the steps of lipid elongation mediated by the retina's ELOVL4 enzyme and to delay or prevent degeneration. We report the synthesis of a VLC-PUFA (32:6 n-3) in sufficient quantity to study its bioavailability and functional benefits in the mouse retina. We acutely and chronically gavage fed wild-type mice and Elovl4 rod-cone conditional knockout mice this synthetic VLC-PUFA to understand its bioavailability and its role in visual function. VLC-PUFA-fed wild-type and Elovl4 conditional knockout mice show a significant increase in retinal VLC-PUFA levels in comparison to controls. The VLC-PUFA-fed mice also had improvement in the animals' visual acuity and electroretinography measurements. Further studies with synthetic VLC-PUFAs will continue to expand our understanding of the physiological roles of these unique retinal lipids, particularly with respect to their potential utility for the treatment and prevention of retinal degenerative diseases.

A ROD-CONE DYSTROPHY IS SYSTEMATICALLY ASSOCIATED TO THE RTN4IP1 RECESSIVE OPTIC ATROPHY.

RTN4IP1 biallelic mutations cause a recessive optic atrophy, sometimes associated to more severe neurological syndromes, but so far, no retinal phenotype has been reported in RTN4IP1 patients, justifying their reappraisal. Seven patients from four families carrying biallelic RTN4IP1 variants were retrospectively reviewed, with emphasis on their age of onset, visual acuity, multimodal imaging including color and autofluorescence frames, spectral-domain optical coherence tomography with RNFL and macular analyses. Seven patients from four RTN4IP1 families developed in their first decade of life a bilateral recessive optic atrophy with severe central visual loss, and primary nystagmus developed in 5 of 7 patients. Six patients were legally blind. In a second stage, the seven individuals developed a rod-cone dystrophy, sparing the macular zone and the far periphery. This retinal damage was identified by 55° field fundus autofluorescence frames and also by spectral-domain optical coherence tomography scans of the temporal part of the macular zone in five of the seven patients. Full-field electroretinography measurements disclosed reduced b-wave amplitude of the rod responses in all patients but two. Family 4 with the p.R103H and c.601A > T (p.K201*) truncating mutation had further combined neurological signs with cerebellar ataxia, seizures, and intellectual disability. RTN4IP1 recessive optic atrophy is systematically associated to a rod-cone dystrophy, which suggests that both the retinal ganglion cells and the rods are affected as a result of a deficit in the mitochondrial respiratory chain. Thus, systematic widefield autofluorescence frames and temporal macular scans are recommended for the evaluation of patients with optic neuropathies.

Electroretinography may reveal cognitive impairment among a cohort of subjects at risk of a major psychiatric disorder

IntroductionAlmost a third of the offspring of parents diagnosed with schizophrenia or bipolar disorder could develop a mental disorder or related symptoms. The objectives of this study were to test the existence of two distinct subgroups of youth at-risk, according to their retinal response to luminance measured with electroretinography (ERG), and to relate the resulting cluster memberships with the cognitive clusters previously reported. MethodologyA clustering analysis was performed with ERG measurements in 107 at-risk offspring. Each subgroup was compared to a healthy control group of 203 individuals. The ERG subgroup memberships were then associated with the cognitive clusters. ResultsA two-cluster solution was obtained: HR-Cluster1 (n=53) showed a control-like ERG profile and HR-Cluster2 (n=54) showed reduced rod amplitudes and prolonged cone latencies of the b-wave. Subjects in the HR-Cluster2 were 2.7 times more likely to belong to the most detrimental cognitive subgroup than subjects in the HR-Cluster1 (49% Vs 18%). ConclusionAt-risk offspring showed two distinct ERG profiles: a control-like and an altered profile. A higher risk of impaired cognitive function was observed in subjects with the altered ERG profile, suggesting the ERG as a potential biomarker of susceptibility to mental illness among youth at risk.

Evolutionary constraints on flicker fusion frequency in Lepidoptera.

Flying insects occupy both diurnal and nocturnal niches, and their visual systems encounter distinct challenges in both conditions. Visual adaptations, such as superposition eyes of moths, enhance sensitivity to low light levels but trade off with spatial and temporal resolution. Conversely, apposition eyes of butterflies enable high spatial resolution but are poorly sensitive in dim light. Although diel activity patterns of insects influence visual processing, their role in evolution of visual systems is relatively unexplored. Lepidopteran insects present an excellent system to study how diel activity patterns and phylogenetic position influence the visual transduction system. We addressed this question by comparing electroretinography measurements of temporal response profiles of diverse Lepidoptera to light stimuli that were flickering at different frequencies. Our data show that the eyes of diurnal butterflies are sensitive to visual stimuli of higher temporal frequencies than nocturnal moths. Hesperiid skippers, which are typically diurnal or crepuscular, exhibit intermediate phenotypes with peak sensitivity across broader frequency range. Across all groups, species within families exhibited similar phenotypes irrespective of diel activity. Thus, Lepidopteran photoreceptors may have diversified under phylogenetic constraints, and shifts in their sensitivity to higher temporal frequencies occurred concomitantly with the evolution of diurnal lifestyles.

Morphological and functional condition of the macula after different types of phaco cataract surgeries

To evaluate morphological and functional condition of the macular area after different types of phaco cataract surgeries. Two groups were formed for comparative study in accordance with criteria for standardization and maximum mitigation of the impact of other factors on the condition of the retina - with standard ultrasound and hybrid (femtolaser-assisted) phacoemulsification (30 operations in each group). Examinations were performed initially, then 7-10 days, and 2-3 month after the surgery. Optical coherence tomography (OCT) and multifocal electroretinography (mfERG) were performed for evaluation of the morphological and functional condition of the macular area. There was no statistically significant dependence of linear and volumetric measures in the macular area on phaco surgery method, and the few variations were most likely related to increasing the time of ultrasound action in standard phacoemulsification. Revealed changes turned out to be significantly less marked than what is considered critical for development of macular edema. Improvement of baseline multifocal electroretinography measurements (increase of the density of retinal biopotential and decrease of latent time) just after the surgery results from the effect the lens opacification has on basic parameters, regardless of phacoemulsification technique. There were no significant differences in postsurgical measurements of multifocal electroretinography obtained in similar periods of postsurgical assessment after standard ultrasound and hybrid phacoemulsification. The results prove the safety of phaco surgery methods and the absence of negative impact of femtolaser component of hybrid phacoemulsification on structural and functional condition of central retina.

Comparison of electroretinographic measurements between tabletop and handheld stimulators in healthy subjects

To compare full-field electroretinography (ffERG) parameters obtained from handheld and tabletop electroretinography (ERG) devices in normal subjects. Twenty volunteers underwent ffERG using a tabletop and handheld stimulator. The responses obtained from the right eyes were compared. The coefficient of variation and intraclass correlation coefficient (ICC) were derived to assess inter- and intra-individual reliability. The b-wave in the rod response, a- and b-waves in the maximal combined response, a-wave in the cone response, and the 30-Hz flicker response showed significantly greater amplitudes when recorded with the tabletop stimulator than with the handheld stimulator. The implicit time of response (ITR) in the 30-Hz flicker response was longer when recorded with the handheld stimulator than when recorded with the tabletop stimulator. With regard to amplitude, the ICC indicated moderate-to-high reliability in the measurement of the b-wave in the rod response, and a- and b-waves in the maximal combined response. With regard to ITR, measurement of the b-wave in the rod response and a-wave in the maximal combined response showed moderate-to-high reliability. Despite the significantly lower ERG amplitude measurements recorded by the handheld stimulator, there were no significant differences in variability between the two stimulators.

Brain-derived neurotrophic factor modulates neuronal network structure and dynamics in striatal cultures: Implications for Huntington's disease

Almost a third of the offspring of parents diagnosed with schizophrenia or bipolar disorder could develop a mental disorder or related symptoms. The objectives of this study were to test the existence of two distinct subgroups of youth at-risk, according to their retinal response to luminance measured with electroretinography (ERG), and to relate the resulting cluster memberships with the cognitive clusters previously reported.A clustering analysis was performed with ERG measurements in 107 at-risk offspring. Each subgroup was compared to a healthy control group of 203 individuals. The ERG subgroup memberships were then associated with the cognitive clusters.A two-cluster solution was obtained: HR-Cluster1 (n=53) showed a control-like ERG profile and HR-Cluster2 (n=54) showed reduced rod amplitudes and prolonged cone latencies of the b-wave. Subjects in the HR-Cluster2 were 2.7 times more likely to belong to the most detrimental cognitive subgroup than subjects in the HR-Cluster1 (49% Vs 18%).At-risk offspring showed two distinct ERG profiles: a control-like and an altered profile. A higher risk of impaired cognitive function was observed in subjects with the altered ERG profile, suggesting the ERG as a potential biomarker of susceptibility to mental illness among youth at risk.

Different effects of various anti-angiogenic treatments in an experimental mouse model of retinopathy of prematurity.

Anti-vascular endothelial growth factor (VEGF) drugs are an option for the treatment of retinopathy of prematurity (ROP). Blocking of other angiogenic factors is also of interest. We therefore investigated in which effects would result blocking of placental growth factor (PlGF). C57BL/6 mice were exposed to 75% oxygen from P7 to P12. Intravitreal injections were performed at P12. Mice of control groups remained untouched after oxygen treatment, or phosphate buffered saline or neutral IgG molecules were injected. In the treatment groups, antibodies against VEGF or PlGF, a mixture of anti-VEGF and anti-PlGF, aflibercept or sunitinib were injected. On P17, electroretinographic (ERG) measurements were performed. Avascular zones and neovascularization were evaluated in retinal flat-mounts. Results are expressed as percent of total retinal area (median with median absolute deviation, MAD). Eyes of control groups showed similar neovascularization (1.4-3.3%, MAD 0.4-0.9%). Neovascularization was significantly less (0.5-0.7%, MAD 0.1-0.3%) in all treatment groups. Avascular zones in the retinas of control groups showed similar values (18.3-25.7%, MAD 4.8-8.8%). Avascular zones were significantly reduced down to 3.6 ± 1.3% after anti-VEGF injection, but they were not reduced significantly in the other treatment groups (13.3-22%, MAD 3.6-6.1%). ERG measurements did not reveal significant differences between the controls and the treatment groups. Blocking of PlGF or injection of sunitinib results in a similar inhibition of neovascularization as by anti-VEGF treatment in the mouse model of ROP. However, physiological angiogenesis that occurs after anti-VEGF treatment is blocked by anti-PlGF or sunitinib treatment, indicating that pathological neovascularization may follow different pathways than physiological angiogenesis.

Soft transparent graphene contact lens electrodes for conformal full-cornea recording of electroretinogram

Visual electrophysiology measurements are important for ophthalmic diagnostic testing. Electrodes with combined optical transparency and softness are highly desirable, and sometimes indispensable for many ocular electrophysiology measurements. Here we report the fabrication of soft graphene contact lens electrodes (GRACEs) with broad-spectrum optical transparency, and their application in conformal, full-cornea recording of electroretinography (ERG) from cynomolgus monkeys. The GRACEs give higher signal amplitude than conventional ERG electrodes in recordings of various full-field ERG responses. High-quality topographic mapping of multifocal ERG under simultaneous fundus monitoring is realized. A conformal and tight interface between the GRACEs and cornea is revealed. Neither corneal irritation nor abnormal behavior of the animals is observed after ERG measurements with GRACEs. Furthermore, spatially resolved ERG recordings on rabbits with graphene multi-electrode array reveal a stronger signal at the central cornea than the periphery. These results demonstrate the unique capabilities of the graphene-based electrodes for in vivo visual electrophysiology studies.

T29. ELECTRORETINOGRAPHIC RESPONSE IN YOUTHS AT GENETIC RISK OF SCHIZOPHRENIA AND BIPOLAR DISORDER AND IN NORMAL CONTROLS: TRANSVERSAL AND LONGITUDINAL DIFFERENCES AND IMPLICATIONS FOR THE RISK TRAJECTORY

BackgroundVisual defects have been widely reported in major psychosis. This includes altered eye tracking, retinal thinning and electrophysiological anomalies.1 One of the most replicated alterations is decreased electroretinographic (ERG) responses that are observed in both bipolar disorder and schizophrenia. Our previous study showed a diminished rod b-wave amplitude in a small sample of children born to an affected parent.2 The fact that an anomaly found in patients would also be observed in children at genetic risk suggests a neurodevelopmental origin and may represent a vulnerability marker. Little data exists on the stability of ERG measures in childhood and adolescence. We wanted to evaluate rod and cone ERG response in larger samples of young offspring of an affected parent (HR) and age and gender balanced controls. By comparing a subsample of 33 offspring to controls, we were able to evaluate the stability and change of ERG over time.MethodsERGs of 71 offspring (mean age of 19 y.o.) and 224 healthy controls (mean age of 20 y.o.) was recorded. From this sample, 33 HR and 26 healthy controls had ERG recordings at 2 different moments (mean interval of 4 years). We then compared the amplitudes obtained at Time 1 and Time 2 in order to assess whether the ERG amplitudes remained stable or varied over time.ResultsCongruent with our 2010 report, this larger HR sample showed a reduced rod b-wave amplitude (p<.05). Probably due to higher statistical power, two other differences were found: an increased cone b-wave latency (p<.05) as well as a diminished mixed rod/cone ERG amplitude (p <.05). None of the ERG amplitudes of the healthy controls changed over time. In contrast, 12 out of 33 HR participant showed a variation of more than one standard deviation (either increase or decrease) on the rod b-wave amplitude which was significantly more frequent than in healthy controls (2/26; p<.05). Change in offspring occurred in both directions: some of them had an increased ERG amplitude response that was sufficient to end up in the confidence interval of the controls whereas others experienced a decreased of their rod amplitude over time.DiscussionThese young high-risk offspring displayed three ERG anomalies that we have already reported in adult patients.2 Our finding bolstered the evidence that ERG anomalies observed in patients may have neurodevelopmental or childhood roots. We observed only little variation in the ERG of the healthy controls over time in that early age range and this appears concordant with existing literature. Of particular interest is the finding that rod b-wave amplitudes were diminished in patients and in offspring. The offspring also showed increased variability over time in comparison to controls. Future studies will seek to understand the relationship between the transversal or longitudinal patterns of rod b-wave amplitudes, as an indicator of risk, and the risk endophenotypes previously reported in the children born to an affected parent.3,4

Avis d’experts pour le traitement des uvéites non infectieuses

Conventional immunosuppressive drugs, anti-TNF alpha and other biotherapies used in clinical practice are capable of controlling non-infectious anterior uveitis, posterior uveitis and panuveitis. The present work has been led by a multidisciplinary panel of experts, internists, rheumatologists and ophthalmologists and is based on a review of the literature. In case of corticodependency or sight-threatening disease, conventional immunosuppressive drugs (methotrexate, azathioprine and mycophenolate mofetil) and/or anti-TNF alpha (adalimumab, infliximab) are used to achieve and maintain remission. Interferon is an efficient immunomodulatory treatment, as a second-line therapy, for some therapeutic indications (refractory macular edema, Behçet's vascularitis). Other biologics, especially tocilizumab, are showing promising results. Local treatments (corticosteroids, sirolimus etc.) are adjuvant therapies in case of unilateral inflammatory relapse. Therapeutic response must be evaluated precisely by clinical examination and repeated complementary investigations (laser flare photometry, multimodal imaging, perimetry, electroretinography measures).

Cerebral malaria induces electrophysiological and neurochemical impairment in mice retinal tissue: possible effect on glutathione and glutamatergic system

BackgroundCerebral malaria (CM) is a severe complication resulting from Plasmodium falciparum infection. This condition has usually been associated with cognitive, behavioural and motor dysfunctions, being the retinopathy the most serious consequence resulting from the disease. The pathophysiological mechanisms underlying this complication remain incompletely understood. Several experimental models of CM have already been developed in order to clarify those mechanisms related to this syndrome. In this context, the present work has been performed to investigate which possible electrophysiological and neurochemistry alterations could be involved in the CM pathology.MethodsExperimental CM was induced in Plasmodium berghei-infected male and female C57Bl/6 mice. The survival and neurological symptoms of CM were registered. Brains and retina were assayed for TNF levels and NOS2 expression. Electroretinography measurements were recorded to assessed a- and b-wave amplitudes and neurochemicals changes were evaluated by determination of glutamate and glutathione levels by HPLC.ResultsSusceptible C57Bl/6 mice infected with ≈ 106 parasitized red blood cells (P. berghei ANKA strain), showed a low parasitaemia, with evident clinical signs as: respiratory failure, ataxia, hemiplegia, and coma followed by animal death. In parallel to the clinical characterization of CM, the retinal electrophysiological analysis showed an intense decrease of a- and-b-wave amplitude associated to cone photoreceptor response only at the 7 days post-infection. Neurochemical results demonstrated that the disease led to a decrease in the glutathione levels with 2 days post inoculation. It was also demonstrated that the increase in the glutathione levels during the infection was followed by the increase in the 3H-glutamate uptake rate (4 and 7 days post-infection), suggesting that CM condition causes an up-regulation of the transporters systems. Furthermore, these findings also highlighted that the electrophysiological and neurochemical alterations occurs in a manner independent on the establishment of an inflammatory response, once tumour necrosis factor levels and inducible nitric oxide synthase expression were altered only in the cerebral tissue but not in the retina.ConclusionsIn summary, these findings indicate for the first time that CM induces neurochemical and electrophysiological impairment in the mice retinal tissue, in a TNF-independent manner.