Characterization of proliferative, glial and angiogenic responses after a CoCl2-induced injury of photoreceptor cells in the adult zebrafish retina

The adult zebrafish is considered a useful model for studying mechanisms involved in tissue growth and regeneration. We have characterized cytotoxic damage to the retina of adult zebrafish caused by the injection of cobalt chloride (CoCl2) into the vitreous cavity. The CoCl2 concentration we used primarily caused injury to photoreceptors. We observed the complete disappearance of cones, followed by rods, across the retina surface from 28 to 96 hr after CoCl2 injury. The loss of 30% of bipolar cells was also observed by 50 hr after lesion (hpl). CoCl2 injury provoked a strong induction of the proliferative activity of multipotent Müller glia and derived progenitors. The effect of CoCl2 on retina cells was significantly reduced by treatment with glutamate ionotropic receptor antagonists. Cone photoreceptor regeneration occurred 25 days after injury. Moreover, a single dose of CoCl2 induced vascular damage and regeneration, whereas three injections of CoCl2 administered weekly provoked neovascular-like changes 20 days after injury. CoCl2 injury also caused microglial reactivity in the optic disc, retina periphery and fibre layer. CoCl2-induced damage enhanced pluripotency and proneural transcription factor gene expression in the mature retina 72 hpl. Tumour necrosis factor alpha, vascular endothelial growth factor (VEGF) and VEGF receptor mRNA levels were also significantly enhanced by 72 hpl. The injury paradigm we have described in this work may be useful for the discovery of signalling molecules and pathways that participate in the regenerative response and it may serve as a model to screen for compounds that could potentially treat aberrant angiogenesis.Fil: Medrano, Matias. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; ArgentinaFil: Pisera Fuster, Antonella. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; ArgentinaFil: Sanchis, Pablo Antonio. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; ArgentinaFil: Paez, Natalia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; ArgentinaFil: Bernabeu, Ramon Oscar. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; ArgentinaFil: Faillace, Maria Paula. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; Argentin

ISCEV standard for clinical multifocal electroretinography (mfERG) (2021 update)

The multifocal electroretinogram (mfERG) is an electrophysiological test that allows the function of multiple discrete areas of the retina to be tested simultaneously. This document, from the International Society for Clinical Electrophysiology of Vision (ISCEV), presents an updated and revised ISCEV standard for clinical mfERG and defines minimum protocols for basic clinical mfERG recording and reporting so that responses can be recognized and compared from different laboratories worldwide. The major changes compared with the previous mfERG standard relate to the minimum length of m-sequences used for recording, reporting of results and a change in document format, to be more consistent with other ISCEV standards

Comparison of 5-year progression of retinitis pigmentosa involving the posterior pole among siblings by means of SD-OCT: a retrospective study

The blockchain technology promises to transform finance, money and evengovernments. However, analyses of blockchain applicability and robustness typicallyfocus on isolated systems whose actors contribute mainly by running the consensusalgorithm. Here, we highlight the importance of considering trustless platformswithin the broader ecosystem that includes social and communication networks. Asan example, we analyse the flash-crash observed on 21st June 2017 in the Ethereumplatform and show that a major phenomenon of social coordination led to acatastrophic cascade of events across several interconnected systems. We proposethe concept of “emergent centralisation” to describe situations where a single systembecomes critically important for the functioning of the whole ecosystem, and arguethat such situations are likely to become more and more frequent in interconnectedsocio-technical systems. We anticipate that the systemic approach we propose willhave implications for future assessments of trustless systems and call for the attentionof policy-makers on the fragility of our interconnected and rapidly changing world

Morphological and Functional Changes in the Retina after Chronic Oxygen-Induced Retinopathy

The mouse model of oxygen-induced retinopathy (OIR) has been widely used for studies of retinopathy of prematurity (ROP). This disorder, characterized by abnormal vascularization of the retina, tends to occur in low birth weight neonates after exposure to high supplemental oxygen. Currently, the incidence of ROP is increasing because of increased survival of these infants due to medical progress. However, little is known about changes in the chronic phase after ROP. Therefore, in this study, we examined morphological and functional changes in the retina using a chronic OIR model. Both the a- and b-waves in the OIR model recovered in a time-dependent manner at 4 weeks (w), 6 w, and 8 w, but the oscillatory potential (OP) amplitudes remained depressed following a return to normoxic conditions. Furthermore, decrease in the thicknesses of the inner plexiform layer (IPL) and inner nuclear layer (INL) at postnatal day (P) 17, 4 w, and 8 w and hyperpermeability of blood vessels were observed in conjunction with the decrease in the expression of claudin-5 and occludin at 8 w. The chronic OIR model revealed the following: (1) a decrease in OP amplitudes, (2) morphological abnormalities in the retinal cells (limited to the IPL and INL) and blood vessels, and (3) an increase in retinal vascular permeability via the impairment of the tight junction proteins. These findings suggest that the experimental animal model used in this study is suitable for elucidating the pathogenesis of ROP and may lead to the development of potential therapeutic agents for ROP treatment

Histological Evaluation of Diabetic Neurodegeneration in the Retina of Zucker Diabetic Fatty (ZDF) Rats

In diabetes, retinal dysfunctions exist prior to clinically detectable vasculopathy, however the pathology behind these functional deficits is still not fully established. Previously, our group published a detailed study on the retinal histopathology of type 1 diabetic (T1D) rat model, where specific alterations were detected. Although the majority of human diabetic patients have type 2 diabetes (T2D), similar studies on T2D models are practically absent. To fill this gap, we examined Zucker Diabetic Fatty (ZDF) rats - a model for T2D - by immunohistochemistry at the age of 32 weeks. Glial reactivity was observed in all diabetic specimens, accompanied by an increase in the number of microglia cells. Prominent outer segment degeneration was detectable with changes in cone opsin expression pattern, without a decrease in the number of labelled elements. The immunoreactivity of AII amacrine cells was markedly decreased and changes were detectable in the number and staining of some other amacrine cell subtypes, while most other cells examined did not show any major alterations. Overall, the retinal histology of ZDF rats shows a surprising similarity to T1D rats indicating that despite the different evolution of the disease, the neuroretinal cells affected are the same in both subtypes of diabetes

Binocular summation and other forms of non-dominant eye contribution in individuals with strabismic amblyopia during habitual viewing

YesAdults with amblyopia ('lazy eye'), long-standing strabismus (ocular misalignment) or both typically do not experience visual symptoms because the signal from weaker eye is given less weight than the signal from its fellow. Here we examine the contribution of the weaker eye of individuals with strabismus and amblyopia with both eyes open and with the deviating eye in its anomalous motor position. The task consisted of a blue-on-yellow detection task along a horizontal line across the central 50 degrees of the visual field. We compare the results obtained in ten individuals with strabismic amblyopia with ten visual normals. At each field location in each participant, we examined how the sensitivity exhibited under binocular conditions compared with sensitivity from four predictions, (i) a model of binocular summation, (ii) the average of the monocular sensitivities, (iii) dominant-eye sensitivity or (iv) non-dominant-eye sensitivity. The proportion of field locations for which the binocular summation model provided the best description of binocular sensitivity was similar in normals (50.6%) and amblyopes (48.2%). Average monocular sensitivity matched binocular sensitivity in 14.1% of amblyopes' field locations compared to 8.8% of normals'. Dominant-eye sensitivity explained sensitivity at 27.1% of field locations in amblyopes but 21.2% in normals. Non-dominant-eye sensitivity explained sensitivity at 10.6% of field locations in amblyopes but 19.4% in normals. Binocular summation provided the best description of the sensitivity profile in 6/10 amblyopes compared to 7/10 of normals. In three amblyopes, dominant-eye sensitivity most closely reflected binocular sensitivity (compared to two normals) and in the remaining amblyope, binocular sensitivity approximated to an average of the monocular sensitivities. Our results suggest a strong positive contribution in habitual viewing from the non-dominant eye in strabismic amblyopes. This is consistent with evidence from other sources that binocular mechanisms are frequently intact in strabismic and amblyopic individuals

Full field electroretinogram in autism spectrum disorder

Purpose To explore early findings that individuals with autism spectrum disorder (ASD) have reduced scotopic ERG b-wave amplitudes. Methods Dark adapted (DA) ERGs were acquired to a range of flash strengths, (-4.0 to 2.3 log phot cd.s.m-2), including and extending the ISCEV standard, from two subject groups: (ASD) N=11 and (Control) N=15 for DA and N=14 for light adapted (LA) ERGs who were matched for mean age and range. Naka-Rushton curves were fitted to DA b-wave amplitude growth over the first limb (-4.0 to -1.0 log phot cd.s.m-2). The derived parameters (Vmax, Km and n) were compared between groups. Scotopic 15 Hz flicker ERGs (14.93Hz) were recorded to 10 flash strengths presented in ascending order from -3.0 to 0.5 log Td.s to assess the slow and fast rod pathways respectively. LA ERGs were acquired to a range of flash strengths, (-0.5 to 1.0 log phot cd.s.m-2). Photopic 30 Hz, flicker ERGs, oscillatory potentials (OPs) and the responses to prolonged 120 ms ON- OFF stimuli were also recorded. Results For some individuals the DA b-wave amplitudes fell below the control 5th centile of the controls with up to four ASD participants (36%) at the 1.5 log phot cd.s.m-2 flash strength and two (18%) ASD participants at the lower -2 log phot cd.s.m-2 flash strength. However, across the thirteen flash strengths there were no significant group differences for b-wave amplitude’s growth (repeated measures ANOVA p=0.83). Nor were there any significant differences between the groups for the Naka-Rushton parameters (p>0.09). No group differences were observed in the 15Hz scotopic flicker phase or amplitude (p>0.1), DA ERG a- wave amplitude or time to peak (p>26). The DA b-wave time to peak at 0.5 log phot cd.s.m-2 were longer in the ASD group (corrected p=0.04). The single ISCEV LA 0.5 log phot cd.s.m-2 (p0.08) to the single flash stimuli although there was a significant interaction between group and flash strength for the b-wave amplitude (corrected p=0.006). The prolonged 120 ms ON-responses were smaller in the ASD group (corrected p=0.003), but the OFF response amplitude (p>0.6) and ON and OFF times to peaks (p>0.4) were similar between groups. The LA OPs showed an earlier bifurcation of OP2 in the younger ASD participants, however no other differences were apparent in the OPs or 30Hz flicker waveforms. Conclusion Some ASD individuals show subnormal DA ERG b-wave amplitudes. Under LA conditions the b-wave is reduced across the ASD group along with the ON response of the ERG. These exploratory findings, suggest there is altered cone-ON bipolar signalling in ASD

A Limited Role for Suppression in the Central Field of Individuals with Strabismic Amblyopia.

yesBackground: Although their eyes are pointing in different directions, people with long-standing strabismic amblyopia typically do not experience double-vision or indeed any visual symptoms arising from their condition. It is generally believed that the phenomenon of suppression plays a major role in dealing with the consequences of amblyopia and strabismus, by preventing images from the weaker/deviating eye from reaching conscious awareness. Suppression is thus a highly sophisticated coping mechanism. Although suppression has been studied for over 100 years the literature is equivocal in relation to the extent of the retina that is suppressed, though the method used to investigate suppression is crucial to the outcome. There is growing evidence that some measurement methods lead to artefactual claims that suppression exists when it does not. Methodology/Results: Here we present the results of an experiment conducted with a new method to examine the prevalence, depth and extent of suppression in ten individuals with strabismic amblyopia. Seven subjects (70%) showed no evidence whatsoever for suppression and in the three individuals who did (30%), the depth and extent of suppression was small. Conclusions: Suppression may play a much smaller role in dealing with the negative consequences of strabismic amblyopia than previously thought. Whereas recent claims of this nature have been made only in those with micro-strabismus our results show extremely limited evidence for suppression across the central visual field in strabismic amblyopes more generally. Instead of suppressing the image from the weaker/deviating eye, we suggest the visual system of individuals with strabismic amblyopia may act to maximise the possibilities for binocular co-operation. This is consistent with recent evidence from strabismic and amblyopic individuals that their binocular mechanisms are intact, and that, just as in visual normals, performance with two eyes is better than with the better eye alone in these individuals