Physiological Effects of Superoxide Dismutase on Altered Visual Function of Retinal Ganglion Cells in db/db Mice

Background: The C57BLKS/J db/db (db/db) mouse is a widely used type 2 diabetic animal model, and this model develops early inner retinal neuronal dysfunction beginning at 24 weeks. The neural mechanisms that mediate early stage retinal dysfunction in this model are unknown. We evaluated visual response properties of retinal ganglion cells (RGCs) during the early stage of diabetic insult (8, 12, and 20 wk) in db/db mice and determined if increased oxidative stress plays a role in impaired visual functions of RGCs in 20 wk old db/db mice. Methodology/Principal Findings: In vitro extracellular single-unit recordings from RGCs in wholemount retinas were performed. The receptive field size, luminance threshold, and contrast gain of the RGCs were investigated. Although ONand OFF-RGCs showed a different time course of RF size reduction, by 20 wk, the RF of ON- and OFF-RGCs were similarly affected. The LT of ON-RGCs was significantly elevated in 12 and 20 wk db/db mice compared to the LT of OFF-RGCs. The diabetic injury also affected contrast gains of ON- and OFF-RGCs differently. The generation of reactive oxidative species (ROS) in fresh retina was estimated by dihydroethidium. Superoxide dismutase (SOD) (300 unit/ml) was applied in Ames medium to the retina, and visual responses of RGCs were recorded for five hours. ROS generation in the retinas of db/db mice increased at 8wk and continued to progress at 20 wk of ages. In vitro application of SOD improved visual functions in 20 wk db/db mice but the SOD treatment affected ON- and OFF-RGCs differently in db/m retina

Pan-retinal characterisation of Light Responses from Ganglion Cells in the Developing Mouse Retina

International audienceWe have investigated the ontogeny of light-driven responses in mouse retinal ganglion cells (RGCs). Using a large-scale, high-density multielectrode array, we recorded from hundreds to thousands of RGCs simultaneously at pan-retinal level, including dorsal and ventral locations. Responses to di erent contrasts not only revealed a complex developmental pro le for ON, OFF and ON-OFF responses, but also unveiled di erences between dorsal and ventral RGC responses. At eye-opening, dorsal RGCs of all types were more responsive to light, perhaps indicating an environmental priority to nest viewing for pre-weaning pups. The developmental pro le of ON and OFF responses exhibited antagonistic behaviour, with the strongest ON responses shortly after eye-opening, followed by an increase in the strength of OFF responses later on. Further, we found that with maturation receptive eld (RF) center sizes decrease, spike-triggered averaged responses to white noise become stronger, and centers become more circular while maintaining di erences between RGC types. We conclude that the maturation of retinal functionality is not spatially homogeneous, likely re ecting ecological requirements that favour earlier maturation of the dorsal retina

Melanopsin-Driven Light Adaptation in Mouse Vision

Background In bright light, mammals use a distinct photopigment (melanopsin) to measure irradiance for centrally mediated responses such as circadian entrainment. We aimed to determine whether the information generated by melanopsin is also used by the visual system as a signal for light adaptation. To this end, we compared retinal and thalamic responses to a range of artificial and natural visual stimuli presented using spectral compositions that either approximate the mouse’s experience of natural daylight (“daylight”) or are selectively depleted of wavelengths to which melanopsin is most sensitive (“mel-low”). Results We found reproducible and reversible changes in the flash electroretinogram between daylight and mel-low. Simultaneous recording in the dorsal lateral geniculate nucleus (dLGN) revealed that these reflect changes in feature selectivity of visual circuits in both temporal and spatial dimensions. A substantial fraction of units preferred finer spatial patterns in the daylight condition, while the population of direction-sensitive units became tuned to faster motion. The dLGN contained a richer, more reliable encoding of natural scenes in the daylight condition. These effects were absent in mice lacking melanopsin. Conclusions The feature selectivity of many neurons in the mouse dLGN is adjusted according to a melanopsin-dependent measure of environmental brightness. These changes originate, at least in part, within the retina. Melanopsin performs a role analogous to a photographer’s light meter, providing an independent measure of irradiance that determines optimal setting for visual circuits

STUDY OF TECHNOLOGICAL PROPERTIES OF SUBSTANCE AND BASIC COMPOSITION FOR OBTAINING THE DRUG PRODUCT OF “BIOMAYRIN”

The low-molecular synthetic drugs, used for the treatment of tuberculosis nowadays, are highly toxic and do not have the ability to selectively penetrate into phagocytes; besides, they are quickly removed from the body without providing a prolonged action. To solve the existing problem, modern methods of modifying the properties of biologically active compounds by joint synthesis of antibiotic with high-molecular compounds, by incorporating antituberculosis drugs into the carrier polymers have been applied. These methods have made it possible to purposefully change their physical-chemical and medical-biological properties.The aim of the work is to evaluate the technological properties of the substance of the combined anti-tuberculosis drug “Biomayrin” and to work out its drug product.Materials and methods. The object of the study was the substance of the original medicinal preparation “Biomayrin”, obtained on the basis of high molecular compounds, and synthetic antituberculosis drugs by the molecular design method.Results and discussion. The results of the comparative analysis of technological properties of the biomayrin substance and the prepared capsular masses with the addition of various antifriction agents are shown in the article. The introduction of antifriction agents greatly improved the technological properties of the substance. As a result, the angle of the natural slope decreased from 42.7° to 31–39°, and the fl owability increased to 2.6–3.6 g/s.Conclusion. Thus, the infl uence of various antifriction agents on the technological properties of the substance of the anti-tuberculosis drug “Biomayrin” was investigated, which allowed to work out the optimal composition of the drug product

Pannexin 1 sustains the electrophysiological responsiveness of retinal ganglion cells

Abstract Pannexin 1 (Panx1) forms ATP-permeable membrane channels that play a key role in purinergic signaling in the nervous system in both normal and pathological conditions. In the retina, particularly high levels of Panx1 are found in retinal ganglion cells (RGCs), but the normal physiological function in these cells remains unclear. In this study, we used patch clamp recordings in the intact inner retina to show that evoked currents characteristic of Panx1 channel activity were detected only in RGCs, particularly in the OFF-type cells. The analysis of pattern electroretinogram (PERG) recordings indicated that Panx1 contributes to the electrical output of the retina. Consistently, PERG amplitudes were significantly impaired in the eyes with targeted ablation of the Panx1 gene in RGCs. Under ocular hypertension and ischemic conditions, however, high Panx1 activity permeated cell membranes and facilitated the selective loss of RGCs or stably transfected Neuro2A cells. Our results show that high expression of the Panx1 channel in RGCs is essential for visual function in the inner retina but makes these cells highly sensitive to mechanical and ischemic stresses. These findings are relevant to the pathophysiology of retinal disorders induced by increased intraocular pressure, such as glaucoma