Sex-Specific Retinal Anomalies Induced by Chronic Social Defeat Stress in Mice

Major depressive disorder (MDD) is one of the most common consequences of chronic stress. Still, there is currently no reliable biomarker to detect individuals at risk to develop the disease. Recently, the retina emerged as an effective way to investigate psychiatric disorders using the electroretinogram (ERG). In this study, cone and rod ERGs were performed in male and female C57BL/6 mice before and after chronic social defeat stress (CSDS). Mice were then divided as susceptible or resilient to stress. Our results suggest that CSDS reduces the amplitude of both oscillatory potentials and a-waves in the rods of resilient but not susceptible males. Similar effects were revealed following the analysis of the cone b-waves, which were faster after CSDS in resilient mice specifically. In females, rod ERGs revealed age-related changes with no change in cone ERGs. Finally, our analysis suggests that baseline ERG can predict with an efficacy up to 71% the expression of susceptibility and resilience before stress exposition in males and females. Overall, our findings suggest that retinal activity is a valid biomarker of stress response that could potentially serve as a tool to predict whether males and females will become susceptible or resilient when facing CSDS.

Assessment of retinal photosensitivity as an objective indicator of expression psychodense effect

BACKGROUND: The retina of the eye, with its wide range of neurotransmitter systems, can be the point of application in the action of the psychotropic drugs, given their synaptotropic properties. MATERIALS AND METHODS: In this regard, a complex of studies was carried out with the participation of volunteers to assess the effect of psychotropic substances with a depressing (melatonin, grandaxin, motherwort tincture) type of action on the functional state of the retina, registered by the campimetric method. In the course of the research, the photosensitivity of the retina and its ability to distinguish colors were evaluated. Moreover, the capabilities of the technique made it possible to assess retinal activity in the field of view from 0 to 21. Such an approach can not only demonstrate the interest of retinal cellular elements in the action of substances, but also raise the question of the participation of the visual system in the psychopharmacological effect more broadly. RESULTS: The work of the visual apparatus was studied both in healthy volunteers of different ages and in persons with emotional disorders, which were identified using special questionnaire tests. It was found that violations of the emotional status are often accompanied by a limitation of the photosensitivity of the retina of varying severity. These facts can be interpreted in different ways. On the one hand, violations of visual functions can lead to psychoemotional disorders and be a pathogenetic link in their development, and on the other hand, primary disorders of retinal light and color sensitivity can provoke the development of psychopathology. However, regardless of the pharmacological characteristics of the studied drugs with psychodeprimating activity, the connection between their anti-anxiety effect and changes in visual function seems to be obvious, which allows us to raise the question of the advisability of taking into account the photosensitivity of the retina for a comprehensive assessment of both the mental state of emotionally labile subjects and the pharmacodynamics of psychodemitting drugs. CONCLUSIONS: Thus, it is legitimate to conclude that taking into account the light and color sensitivity of the retina can be one of the quantitative criteria for the severity and effectiveness of psychopharmacotherapy.

Contactless recordings of retinal activity using optically pumped magnetometers

Optically pumped magnetometers (OPMs) have been adopted for the recording of brain activity. Without the need to be cooled to cryogenic temperatures, an array of these sensors can be placed more flexibly, which allows for the recording of neuronal structures other than neocortex. Here we use eight OPM sensors to record human retinal activity following flash stimulation. We compare this magnetoretinographic (MRG) activity to the simultaneously recorded electroretinogram of the eight participants. The MRG shows the familiar flash-evoked potentials (a-wave and b-wave) and shares a highly significant amount of information with the electroretinogram recording (both in a simultaneous and separate recording). We conclude that OPM sensors have the potential to become a contactless alternative to fiber electrodes for the recording of retinal activity. Such a contactless solution can benefit both clinical and neuroscientific settings.

Functional connexin35 increased in the myopic chicken retina

Our previous research showed that increased phosphorylation of connexin (Cx)36 indicated extended coupling of AII amacrine cells (ACs) in the rod-dominant mouse myopic retina. This research will determine whether phosphorylation at serine 276 of Cx35-containing gap junctions increased in the myopic chicken, whose retina is cone-dominant. Refractive errors and ocular biometric dimensions of 7-days-old chickens were determined following 12 h and 7 days induction of myopia by a −10D lens. The expression pattern and size of Cx35-positive plaques were examined in the early (12 h) and compensated stages (7 days) of lens-induced myopia (LIM). At the same time, phosphorylation at serine 276 (functional assay) of Cx35 in strata 5 (S5) of the inner plexiform layer was investigated. The axial length of the 7 days LIM eyes was significantly longer than that of non-LIM controls (P < 0.05). Anti-phospho-Ser276 (Ser276-P)-labeled plaques were significantly increased in LIM retinas at both 12 h and 7 days. The density of Ser276-P of Cx35 was observed to increase after 12 h LIM. In the meanwhile, the areas of existing Cx35 plaques did not change. As there was more phosphorylation of connexin35 at Ser276 at both the early and late stages (12 h) and 7 days of LIM chicken retinal activity, the coupling with ACs could be increased in myopia development of the cone-dominated chicken retina.

Correlation of callosal connections and optical imaging maps in visual cortex of mice lacking retinal activity waves due to deficiency in the ß2 subunit of the nicotinic acetylcholine receptor

Studies of visual callosal connections proposed that bilateral projections from temporal retina promote the formation of callosal linkages between cortical loci that are retinotopically matched and non-mirror symmetric with respect to the brain midline. It is therefore possible for a spontaneously active retinal locus to simultaneously activate retinotopically corresponding loci in both cortices, leading to Hebbian-like stabilization of connections between them before the eyes open. Interhemispheric correlated activity could stem from single ganglion cells that send axon branches to both sides, or from closely located cells that project to one side or the other, but which fire in synchrony due to spontaneously generated retinal activity waves. We hypothesized that lack of retinal waves could induce callosal map anomalies similar to those produced by neonatal enucleation. We studied mice lacking retinal waves due to deficiency in the ß2 subunit of the nicotinic acetylcholine receptor. The organization of callosal projections revealed with small tracer injections was correlated with V1 maps made by imaging intrinsic optical responses to drifting stimuli. Consistent with studies showing that retinofugal and geniculocortical projections are less focused in ß2 -/- mice, we found that the overall callosal pattern in V1 is markedly broader in ß2 -/- mice than in wild type mice. However, the fine topography of the callosal map in ß2 -/- mice is similar to that in wild type and ß2 -/+ mice, indicating that lack of retinal waves is not sufficient for inducing the reversal in the callosal map caused by neonatal enucleation.

Sex-specific retinal anomalies induced by chronic social stress in mice

Major depressive disorder (MDD) is one of the most common consequences of chronic stress. Still, there is currently no reliable biomarker to detect individuals at risk to develop MDD. Recently, the retina emerged as an effective way to approach the brain and investigate psychiatric disorders with the use of the electroretinogram (ERG). In this study, cones and rods ERGs were performed in male and female mice before and after chronic social defeat stress (CSDS). Mice were then divided as susceptible or resilient to stress. Significant results were only observed in rods ERGs. In males, susceptible mice showed prolonged a-wave implicit times at baseline that were shortened after CSDS. The a-wave was also decreased in both susceptible and resilient male mice after CSDS. In females, rod a-waves were shorter in susceptible than in control mice after CSDS resulting from the latter demonstrating delayed a-waves. Baseline ERGs were able to predict – to some extent – the expression of susceptibility and resilience before stress exposition in male and female mice. Overall, our findings suggest that retinal activity is a presumptive biomarker of stress response and that the ERG could potentially serve as a predicting tool of the stress response in mice.

Ignoring correlated activity causes a failure of retinal population codes

From starlight to sunlight, adaptation alters retinal output, changing both the signal and noise among populations of retinal ganglion cells (RGCs). Here we determine how these light level-dependent changes impact decoding of retinal output, testing the importance of accounting for RGC noise correlations to optimally read out retinal activity. We find that at moonlight conditions, correlated noise is greater and assuming independent noise severely diminishes decoding performance. In fact, assuming independence among a local population of RGCs produces worse decoding than using a single RGC, demonstrating a failure of population codes when correlated noise is substantial and ignored. We generalize these results with a simple model to determine what conditions dictate this failure of population processing. This work elucidates the circumstances in which accounting for noise correlations is necessary to take advantage of population-level codes and shows that sensory adaptation can strongly impact decoding requirements on downstream brain areas.

Retinal Response of Low Myopes during Orthokeratology Treatment

The aim of this study was to evaluate the changes in retinal activity during orthokeratology (OK) treatment in 20 myopic eyes. Pattern electroretinography (PERG) and visual evoked potential (VEP) were assessed with the RETI-port/scan21 (Roland Consult, Wiesbaden, Germany). Measurements were taken at baseline (BL) and 1 night (1N), 15 nights (15N), 30 nights (30N), and 60 nights (60N) of OK lens wear. Repeated measures analysis of variance (ANOVA) and the Friedman test were used. Twenty eyes (23.20 ± 3.46 years, 70% female) with visual acuity ≤ 0.00 logMAR in post-treatment showed that despite a slight increase in retinal and cortical response amplitude, observed with both PERG and VEP, respectively, immediately after the initial treatment, these differences found were not statistically significant during the 60 days of OK treatment, despite a statistically significant increase in N95 response with PERG. This shows that retinal and cortical visual-related electrical activity is maintained or slightly increased during OK treatment.