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Summary: In this paper, a family of single‐phase boost AC‐AC converters based on impedance network cells with symmetric bipolar operation is proposed. The proposed converters exhibit a range of voltage gains as a result of non‐inverting and inverting boost operations, which are influenced by the input voltage and various impedance source cells. The converters leverage inherent commutation to address the commutation problem without requiring snubber circuits and safe commutation strategy. Additionally, high‐speed switching is achieved by preventing power MOSFETs' body diode conduction and related poor reverse recovery issues. The design incorporates a simple and flexible switching strategy to produce step‐change frequency at the output, using only four switches to achieve both step‐changed frequency operation and output voltage regulation. Furthermore, by reducing the total stored energy of passive components, the proposed converters effectively decrease volume, weight, and cost. The operational modes of the converters are elucidated, and their key relationships are summarized in tabular format. Finally, experimental validation through a laboratory prototype confirms the performance accuracy of the proposed converters at frequencies 25, 50, and 100 Hz. [ABSTRACT FROM AUTHOR]

Everything that the brain sees must first be encoded by the retina, which maintains a reliable representation of the visual world in many different, complex natural scenes while also adapting to stimulus changes. This study quantifies whether and how the brain selectively encodes stimulus features about scene identity in complex naturalistic environments. While a wealth of previous work has dug into the static and dynamic features of the population code in retinal ganglion cells (RGCs), less is known about how populations form both flexible and reliable encoding in natural moving scenes. We record from the larval salamander retina responding to five different natural movies, over many repeats, and use these data to characterize the population code in terms of single-cell fluctuations in rate and pairwise couplings between cells. Decomposing the population code into independent and cell-cell interactions reveals how broad scene structure is encoded in the retinal output. while the single-cell activity adapts to different stimuli, the population structure captured in the sparse, strong couplings is consistent across natural movies as well as synthetic stimuli. We show that these interactions contribute to encoding scene identity. We also demonstrate that this structure likely arises in part from shared bipolar cell input as well as from gap junctions between RGCs and amacrine cells. [ABSTRACT FROM AUTHOR]

The assembly locking compression force of the fuel cell directly impacts the contact area between the metallic bipolar plate (MBP) and the membrane electrode assembly (MEA), thereby affecting the electrical resistance of the fuel cell stack. In this study, we employed the finite element method to build a fuel cell stack simulation model to analyze the deformation and warpage of the MBP after being subjected to locking force. Through nonlinear contact elements, we showed the contact area and pressure distribution between the MBP and the MEA. The research results indicated that, owing to the effects of bolt locking, the left and right sides of the interface between the MBP and the MEA are the main contact areas transmitting the contact pressure. This area forms the primary support points for the bending load, leading to upward or downward warping deformation, and causes noticeable gaps between the bipolar plates and the MEA. In addition, distorted design features were added to the MBP to compare and improve the deformation of the MBP. The results showed that the bipolar plate with distorted design features can effectively reduce the maximum vertical deformation by 10.3%, which will effectively improve the contact area between the bipolar plate and the MEA module. This will effectively reduce the contact resistance of the fuel cell. [ABSTRACT FROM AUTHOR]

This paper proposes a family of bipolar step‐up cells (BSUCs). Additionally, a family of interleaved parallel isolated high‐gain DC/DC converters with bipolar outputs based on the BSUCs is proposed. Using one of these converters as an example, it is demonstrated that the converter inherits the advantages of DC three‐level characteristics, resulting in low component voltage stress and low output voltage ripple. Moreover, the converter features a low input current ripple, electrical isolation, bipolar outputs, high voltage gain and operates both switches and diodes in a soft‐switching state. Furthermore, the neutral point of the bipolar outputs in this converter possesses self‐balancing characteristics, effectively mitigating the impact of parasitic parameters on voltage balance. Even with a significant deviation of the duty cycles in the main switches, the influence on the neutral point voltage balance remains very slight. Besides, to address the difficulty of accurately calculating output voltage ripple using traditional methods, a voltage ripple calculation method based on linearizing the charging of the output capacitor is proposed, characterized by its high accuracy and simplicity in the calculation process. Finally, an experimental prototype is established to verify the performance of the proposed converter. [ABSTRACT FROM AUTHOR]

Diabetic retinopathy is governed by abnormal apoptosis, increased capillary pressure, and other linked pathology that needs an efficient treatment by multitargeted approaches. Thus, the current study aimed to explore the potential of inhibition of targeted enzymes (DPP4, ACE‐2, and aldose reductase) and free radical scavenging capabilities of selected compounds (nafronyl or naftidrofuryl) through in silico and in vivo investigations. Significant binding energies were observed in complexes of aldolase reductase, angiotensin type 1 receptor, and DPP4 against the nafronyl and sitagliptin more than −7.5 kcal/mol. Further validation of free energy was confirmed by calculations of molecular mechanics Poisson–Boltzmann surface area (MMPBSA), and configurational stabilities examined by PCA (principal component analysis). Additionally, drug‐likeness was examined by the Swiss ADME web tool, which showed significant findings. Consequently, in vivo experimentations showed significant inflammation and alterations in retinal layers of inner plexiform (inner limiting membrane, nerve fibers, and ganglionic cells), inner nuclear layer (bipolar cells and horizontal cells), and photoreceptors cells. Whereas the treatments (nafronyl and sitagliptin) caused significant improvements in the histoarchitecture of the retina. Additionally, the HOMA indices (IR‐insulin resistance, sensitivity, and β cells functioning) and levels of free radicals were significantly altered in the diabetic control group in comparison to intact control. Nafronyl administration showed significant ameliorations in HOMA indices as well as antioxidant levels. Based on the results, it can be concluded that nafronyl efficiently interacts with target enzymes, which may result in potent inhibition and ameliorations in retinal histology as well as glucose homeostasis and antioxidants. [ABSTRACT FROM AUTHOR]

Retinal electrophysiological alterations are implicated in psychosis, but their relationship with cognition in early course psychosis (ECP) is understudied. The Brief Assessment of Cognition (BAC) and flash electroretinography (fERG) were conducted in 24 controls (HC) and 27 ECP individuals. Partial Spearman correlations were performed between fERG and BAC. Lower Photopic-1b and Scotopic-3b amplitudes were identified in ECP vs. HCs. Correlations were significant (p<0.05) between BAC Composite score and a-wave S3a and S2a and b-wave S2b and S3b conditions. Thus, ECP was characterized by lower ERG responses, and lower rod/cone/bipolar cell responses were related to poorer cognition. [ABSTRACT FROM AUTHOR]

In congenital stationary night blindness, type 2 (CSNB2)--a disorder involving the Cav1.4 (L-type) Ca2+ channel--visual impairment is mild considering that Cav1.4 mediates synaptic release from rod and cone photoreceptors. Here, we addressed this conundrum using a Cav1.4 knockout (KO) mouse and a knock-in (G369i KI) mouse expressing a non-conducting Cav1.4. Surprisingly, Cav3 (T-type) Ca2+ currents were detected in cones of G369i KI mice and Cav1.4 KO mice but not in cones of wild-type mouse, ground squirrels, and macaque retina. Whereas Cav1.4 KO mice are blind, G369i KI mice exhibit normal photopic (i.e. cone-mediated) visual behavior. Cone synapses, which fail to form in Cav1.4 KO mice, are present, albeit enlarged, and with some errors in postsynaptic wiring in G369i KI mice. While Cav1.4 KO mice lack evidence of cone synaptic responses, electrophysiological recordings in G369i KI mice revealed nominal transmission from cones to horizontal cells and bipolar cells. In CSNB2, we propose that Cav3 channels maintain cone synaptic output provided that the nonconducting role of Cav1.4 in cone synaptogenesis remains intact. Our findings reveal an unexpected form of homeostatic plasticity that relies on a non-canonical role of an ion channel. [ABSTRACT FROM AUTHOR]

The operation of the retina, like other brain circuits, is under modulatory control. One coordinator of changes in retinal function is dopamine, a neuromodulator released in a light-dependent way to adjust vision on a diurnal cycle. Here, we demonstrate that substance P is a similarly powerful retinal modulator that interacts with the dopamine system. By imaging glutamatergic synaptic transmission in larval zebrafish, we find that substance P decreases the contrast sensitivity of ON and OFF visual channels up to 8-fold, with suppression of visual signals being strongest through the "transient" pathway responding to higher frequencies. These actions are exerted in the morning, in large part by suppressing the amplification of visual signals by dopamine, but substance P is almost completely inactive in the afternoon. Modulation of retinal gain is accompanied by changes in patterns of vesicle release at the synapses of bipolar cells: increased gain shifts coding of stimulus strength from the rate of release events to their amplitude generated by a process of multivesicular release (MVR). Together, these actions of substance P reduce the flow of visual information, measured in bits, ∼3-fold. Thus, whereas dopamine "pushes" the retina to transmit information at higher rates in the afternoon, substance P acts in antiphase to suppress dopamine signaling and "pull down" information transmission in the morning. • Substance P (SP) decreases gain of zebrafish retina and blocks transient pathway • SP acts in the morning and suppresses signal amplification by dopamine • SP adjusts the way vesicles encode stimulus strength at bipolar cell synapses • SP and dopamine interact to adjust diurnal flow of visual information José Moya-Díaz et al. demonstrate that substance P is a powerful retinal modulator that interacts with the dopamine system. While dopamine "pushes" the retina to transmit visual signals at high gain in the afternoon, substance P acts in antiphase to suppress dopamine signaling and "pull down" information transmission in the morning. [ABSTRACT FROM AUTHOR]

In the article, the results of previous research on the problematic issues of the organization and functioning of the human eye retina from a cybernetic point of view are given in a concise form, some of which are confirmed by modeling. In more detail, the organization of individual components of the human visual analyzer is considered, namely, the lateral geniculate nucleus and several areas of the visual cortex. In particular, the transfer of information from different areas of the retina, its placement in the layers of the lateral geniculate nucleus, and the determination of highly dynamic zones in the image for controlling saccades are justified. It is shown that information about the magnitude of the difference of brightness and color is stored in the same difference, and in the brain, there is an exact binding of the points of the differences to the types and location of both bipolar cells and their cones in the retina. A functional linear organization of the architecture of the visual cortex of the brain is proposed for determining the orientation of the lines in the image, which makes it possible to join the lines of one orientation, detect different types of movement, and evaluate the speed of changes in the space of the scene. According to the idea/hypothesis of the columnar organization of neurons, an orientational columnar organization of neurons is proposed, which makes it possible to determine all of the possible orientations of lines at one point in space, i.e., determine the angles, tangents, and intersections of lines, their orientation, coordinates, and dimensions, which are very powerful informative features for searching and recognizing objects and building the frame of the object, as well as its three-dimensional model (under the condition of using information from both eyes). An idea is proposed to restore an actual scene image by coloring the spatial areas of the image using information not only of the contours of the areas, but also of actual brightness values from the foveola and fovea zones of the central fovea. [ABSTRACT FROM AUTHOR]

Retinitis pigmentosa is a hereditary retinal disease that affects rod and cone photoreceptors, leading to progressive photoreceptor loss. Previous research supports the beneficial effect of electrical stimulation on photoreceptor survival. This study aims to identify the most effective electrical stimulation parameters and functional advantages of transcorneal electrical stimulation (tcES) in mice affected by inherited retinal degeneration. Additionally, the study seeked to analyze the electric field that reaches the retina in both eyes in mice and post-mortem humans. In this study, we recorded waveforms and voltages directed to the retina during transcorneal electrical stimulation in C57BL/6J mice using an intraocular needle probe with rectangular, sine, and ramp waveforms. To investigate the functional effects of electrical stimulation on photoreceptors, we used human retinal explant cultures and rhodopsin knockout (Rho–/–) mice, demonstrating progressive photoreceptor degeneration with age. Human retinal explants isolated from the donors' eyes were then subjected to electrical stimulation and cultured for 48 hours to simulate the neurodegenerative environment in vitro. Photoreceptor density was evaluated by rhodopsin immunolabeling. In vivo Rho–/– mice were subjected to two 5-day series of daily transcorneal electrical stimulation using rectangular and ramp waveforms. Retinal function and visual perception of mice were evaluated by electroretinography and optomotor response (OMR), respectively. Immunolabeling was used to assess the morphological and biochemical changes of the photoreceptor and bipolar cells in mouse retinas. Oscilloscope recordings indicated effective delivery of rectangular, sine, and ramp waveforms to the retina by transcorneal electrical stimulation, of which the ramp waveform required the lowest voltage. Evaluation of the total conductive resistance of the post-mortem human compared to the mouse eyes indicated higher cornea-to-retina resistance in human eyes. The temperature recordings during and after electrical stimulation indicated no significant temperature change in vivo and only a subtle temperature increase in vitro (~0.5–1.5°C). Electrical stimulation increased photoreceptor survival in human retinal explant cultures, particularly at the ramp waveform. Transcorneal electrical stimulation (rectangular + ramp) waveforms significantly improved the survival and function of S and M-cones and enhanced visual acuity based on the optomotor response results. Histology and immunolabeling demonstrated increased photoreceptor survival, improved outer nuclear layer thickness, and increased bipolar cell sprouting in Rho–/– mice. These results indicate that transcorneal electrical stimulation effectively delivers the electrical field to the retina, improves photoreceptor survival in both human and mouse retinas, and increases visual function in Rho–/– mice. Combined rectangular and ramp waveform stimulation can promote photoreceptor survival in a minimally invasive fashion. [ABSTRACT FROM AUTHOR]

The organotypic retinal explant culture has been established for more than a decade and offers a range of unique advantages compared with in vivo experiments and cell cultures. However, the lack of systematic and continuous comparison between in vivo retinal development and the organotypic retinal explant culture makes this model controversial in postnatal retinal development studies. Thus, we aimed to verify the feasibility of using this model for postnatal retinal development studies by comparing it with the in vivo retina. In this study, we showed that postnatal retinal explants undergo normal development, and exhibit a consistent structure and timeline with retinas in vivo. Initially, we used SOX2 and PAX6 immunostaining to identify retinal progenitor cells. We then examined cell proliferation and migration by immunostaining with Ki-67 and doublecortin, respectively. Ki-67- and doublecortin-positive cells decreased in both in vivo and explants during postnatal retinogenesis, and exhibited a high degree of similarity in abundance and distribution between groups. Additionally, we used Ceh-10 homeodomain-containing homolog, glutamate-ammonia ligase (glutamine synthetase), neuronal nuclei, and ionized calcium-binding adapter molecule 1 immunostaining to examine the emergence of bipolar cells, Müller glia, mature neurons, and microglia, respectively. The timing and spatial patterns of the emergence of these cell types were remarkably consistent between in vivo and explant retinas. Our study showed that the organotypic retinal explant culture model had a high degree of consistency with the progression of in vivo early postnatal retina development. The findings confirm the accuracy and credibility of this model and support its use for long-term, systematic, and continuous observation.

Radial glia (RG) are the main progenitor cell type in the developing cortex. These cells are highly polarized, with a long basal process spanning the entire thickness of the cortex and acting as a support for neuronal migration. The RG cell terminates by an endfoot that contacts the pial (basal) surface. A shorter apical process also terminates with an endfoot that faces the ventricle, with a primary cilium protruding in the cerebrospinal fluid. These cell domains have particular subcellular compositions that are critical for the correct functioning of RG. When altered, this can affect proper development of the cortex, ultimately leading to cortical malformations, associated with different pathological outcomes. In this review, we focus on the current knowledge concerning the cell biology of these bipolar stem cells and discuss the role of their polarity in health and disease. [ABSTRACT FROM AUTHOR]

Head‐direction (HD) cells are a fundamental component in the hippocampal‐entorhinal circuit for spatial navigation and help maintain an internal sense of direction to anchor the orientation in space. A classical HD cell robustly increases its firing rate when the head is oriented toward a specific direction, with each cell tuned to only one direction. Although unidirectional HD cells are reported broadly across multiple brain regions, computation modelling has predicted the existence of multiple equilibrium states of HD network, which has yet to be proven. In this study, a novel HD variant of bipolar HD cells in the medial entorhinal cortex (MEC) are identified that exhibit stable double‐peaked directional tuning properties. The bipolar patterns remain stable in the darkness and across environments of distinct geometric shapes. Moreover, bipolar HD cells co‐rotate coherently with unipolar HD cells to anchor the external visual cue. The discovery reveals a new spatial cell type of bipolar HD cells, whose unique activity patterns may comprise a potential building block for a sophisticated local neural circuit configuration for the internal representation of direction. These findings may contribute to the understanding of how the brain processes spatial information by shedding light on the role of bipolar HD cells in this process. [ABSTRACT FROM AUTHOR]

An optoelectronic synaptic device with the color‐recognition ability is highly desired for achieving the high‐efficient neuromorphic color visual system. In order to realistically implement the functionality of retina (i.e., bipolar cells and cones photoreceptors), the exploration of multiwavelength controlled optoelectronic synaptic devices with fully light tunable ability would be sorely needed. Here, a multiwavelength controlled plasmonic optoelectronic memristor based on the size‐dependent localized surface plasmon resonance (LSPR) of metallic nanostructures is developed. The distinguishable red (R), green (G), and blue (B) light response behaviors can be achieved in this single device, which enables the realization of color image perception and memory functions. The RGB light‐strengthened synaptic plasticity can be depressed by ultraviolet light stimulations, relying on the effects of LSPR and optical excitation in WOx:Ag nanocomposites. Moreover, the visual attention for color (color discrimination) is realized in this memristor, which promotes the improvement of recognition accuracy during the color image recognition process. A new approach in developing multiwavelength controlled synaptic devices is provided here for highly efficient neuromorphic vision. [ABSTRACT FROM AUTHOR]

Background: Affections of eye are commonly encountered in all the species of animals. The age-related changes of the retina primarily cause loss of visual acuity as well as reduction of the visual field. Hence, the current study was carried out to establish basic data related to ageing changes in the retina of buffaloes. Methods: The study was conducted on 63 eye balls of locally available buffaloes of different breeds. These buffaloes were categorized into 3 groups i.e., group I (1-5 yrs), group II (6-10 yrs) and group III (11 yrs and above). The eyeballs were isolated and fixed with Davidson's fluid. The paraffin sections were subjected for routine histological study. Result: The thickness of retinal pigment epithelium was increased from group I to III buffaloes from 6.06±0.18 to 8.44±0.32 and the quantity of melanin pigment was decreased with advancement of age. Rod and cone cells of the photoreceptor layer were tightly packed in young age, loosely arranged in old animals. The mean thickness (µm) of photoreceptors and outer nuclear layers together was decreased from 64.22±1.84 to 58.72±2.1 with age advancement. The displacement of nuclei from outer nuclear layer into outer plexiform layer was significantly decreased in old animals. The outer limiting membrane was continuous and uninterrupted throughout the life. The thickness of outer plexiform layer was increased with advancement of age from 8.78±0.58 to 10±0.51 due to enhancement of synaptic fibers density. As age advances the number and density of horizontal, bipolar and amacrine cells were decreased and also the mean thickness (µm) of this layer was decreased from 30.83±1.48 to 22.56±0.62 in the inner nuclear layer. The thickness of inner plexiform layer was increased from 42.44±2.23 to 45.39±0.81 with advancement of age due to increased cystoids spaces and thickening of retinal blood vessels. In ganglionic cell layer, the number of β-ganglion cells were more than the β-ganglion cells, their common number were decreased approximately from 16-20 cells/sq.mm to 7-10 cells/sq.mm, whereas the average size was increased from 4.72±0.49 to 15.83±0.83 with advancement of age. In aged buffaloes nerve fiber layer showed corpora amylacea and thickened blood vessels. The inner limiting membrane became thick and uninterrupted in old buffaloes. The total thickness (µm) of retina in group I, II and III buffaloes were 235.5±7.25, 184.33±3.64 and 201.05±5.15 respectively. [ABSTRACT FROM AUTHOR]

Syntaxin 3 is a member of a large protein family of syntaxin proteins that mediate fusion between vesicles and their target membranes. Mutations in the ubiquitously expressed syntaxin 3A splice form give rise to a serious gastrointestinal disorder in humans called microvillus inclusion disorder, while mutations that additionally involve syntaxin 3B, a splice form that is expressed primarily in retinal photoreceptors and bipolar cells, additionally give rise to an early onset severe retinal dystrophy. In this review, we discuss recent studies elucidating the roles of syntaxin 3B and the regulation of syntaxin 3B functionality in membrane fusion and neurotransmitter release in the vertebrate retina. [ABSTRACT FROM AUTHOR]

The retinal fovea in human and nonhuman primates is essential for high acuity and color vision. Within the fovea lies specialized circuitry in which signals from a single cone photoreceptor are largely conveyed to one ON and one OFF type midget bipolar cell (MBC), which in turn connect to a single ON or OFF midget ganglion cell (MGC), respectively. Restoring foveal vision requires not only photoreceptor replacement but also appropriate reconnection with surviving ON and OFF MBCs and MGCs. However, our current understanding of the effects of cone loss on the remaining foveal midget pathway is limited. We thus used serial block-face electron microscopy to determine the degree of plasticity and potential remodeling of this pathway in adult Macaca fascicularis several months after acute photoreceptor loss upon photocoagulation. We reconstructed MBC structure and connectivity within and adjacent to the region of cone loss. We found that MBC dendrites within the scotoma retracted and failed to reach surviving cones to form new connections. However, both surviving cones and ON and OFF MBC dendrites at the scotoma border exhibited remodeling, suggesting that these neurons can demonstrate plasticity and rewiring at maturity. At six months postlesion, disconnected OFF MBCs clearly lost output ribbon synapses with their postsynaptic partners, whereas the majority of ON MBCs maintained their axonal ribbon numbers, suggesting differential timing or extent in ON and OFF midget circuit remodeling after cone loss. Our findings raise rewiring considerations for cell replacement approaches in the restoration of foveal vision. [ABSTRACT FROM AUTHOR]

The neural pathways that start human color vision begin in the complex synaptic network of the foveal retina where signals originating in long (L), middle (M), and short (S) wavelength-sensitive cone photoreceptor types are compared through antagonistic interactions, referred to as opponency. In nonhuman primates, two cone opponent pathways are well established: an L vs. M cone circuit linked to the midget ganglion cell type, often called the red-green pathway, and an S vs. L + M cone circuit linked to the small bistratified ganglion cell type, often called the blue-yellow pathway. These pathways have been taken to correspond in human vision to cardinal directions in a trichromatic color space, providing the parallel inputs to higher-level color processing. Yet linking cone opponency in the nonhuman primate retina to color mechanisms in human vision has proven particularly difficult. Here, we apply connectomic reconstruction to the human foveal retina to trace parallel excitatory synaptic outputs from the S-ON (or "blue-cone") bipolar cell to the small bistratified cell and two additional ganglion cell types: a large bistratified ganglion cell and a subpopulation of ON-midget ganglion cells, whose synaptic connections suggest a significant and unique role in color vision. These two ganglion cell types are postsynaptic to both S-ON and L vs. M opponent midget bipolar cells and thus define excitatory pathways in the foveal retina that merge the cardinal red-green and blue-yellow circuits, with the potential for trichromatic cone opponency at the first stage of human vision. [ABSTRACT FROM AUTHOR]

Spatially nonlinear stimulus integration by retinal ganglion cells lies at the heart of various computations performed by the retina. It arises from the nonlinear transmission of signals that ganglion cells receive from bipolar cells, which thereby constitute functional subunits within a ganglion cell's receptive field. Inferring these subunits from recorded ganglion cell activity promises a new avenue for studying the functional architecture of the retina. This calls for efficient methods, which leave sufficient experimental time to leverage the acquired knowledge for further investigating identified subunits. Here, we combine concepts from super-resolution microscopy and computed tomography and introduce super-resolved tomographic reconstruction (STR) as a technique to efficiently stimulate and locate receptive field subunits. Simulations demonstrate that this approach can reliably identify subunits across a wide range of model variations, and application in recordings of primate parasol ganglion cells validates the experimental feasibility. STR can potentially reveal comprehensive subunit layouts within only a few tens of minutes of recording time, making it ideal for online analysis and closed-loop investigations of receptive field substructure in retina recordings. Author summary: Neural computations in sensory systems often involve nonlinear pooling of sensory information. In the vertebrate retina, nonlinear signal transmission between bipolar cells and downstream ganglion cells, the output neurons of the retina, shapes the ganglion cells' functional properties and structures a ganglion cell's receptive field into smaller subunits. Methods for identifying these subunits from recordings of ganglion cell activity are needed to better understand the signal flow and the computations occurring between bipolar and ganglion cells. We here show that concepts from super-resolution microscopy and tomography can be used to design a visual stimulus and corresponding analysis to efficiently trigger ganglion cell activity while maintaining high spatial resolution for revealing subunits. As demonstrated by computer simulations and recordings from the primate retina, the method can identify subunit layouts with little experimental recording time, providing for the possibility to be combined with in-depth functional analyses or applied in closed-loop experiments. [ABSTRACT FROM AUTHOR]

The current research aimed to investigate the adaptations in eye morphology and the structure of retinal photoreceptors in amphibious fish (Alticus kirkii) and nonamphibious fish (Gambusia affinis) to understand the visual adaptations of A. kirkii upon being out of water. The morphological and histological features of the eyes of both species were adressed. Results showed that A. kirkii exhibits several visual adaptations for seeing in air. Morphologically, the eyes of A. kirkii are bulging and positioned on retractable stalks at the top of the head, unlike those of G. affinis. The ratio of axial length to head length is greater in A. kirkii than in G. affinis. Histologically, the cornea of A. kirkii is more curved than that of G. affinis, with a crooked internal layer that is more curled in A. kirkii and reduced in G. affinis. The lens is larger, slightly flattened, and more stable in A. kirkii compared to G. affinis. The retina is thicker in A. kirkii and consists of 10 layers. In A. kirkii, the external layer of pigmented epithelium is densely packed in the peripheral region of the photoreceptor layer, whereas in G. affinis, it is composed of epithelial cells in the peripheral region but is less thick. The visual cell layer includes simple and double cones; A. kirkii has a greater abundance and larger size of cones compared to G. affinis. The outer nuclear layer, which contains the visual cell bodies, is thicker in A. kirkii than in G. affinis. The outer plexiform layer is narrower in A. kirkii, with higher densities of both bipolar and horizontal cells compared to G. affinis. The inner nuclear layer shows a heterogeneous cell composition and is more crowded in A. kirkii than in G. affinis. Additionally, disparities in the thickness of the inner limiting membrane and nerve fiber layer affect the transmission of signals from the retina to the brain. [ABSTRACT FROM AUTHOR]

In recent research, dendritic neuron-based models have shown promise in effectively learning and recognizing object motion direction within binary images. Leveraging the dendritic neuron structure and On–Off Response mechanism within the primary cortex, this approach has notably reduced learning time and costs compared to traditional neural networks. This paper advances the existing model by integrating bio-inspired components into a learnable dendritic neuron-based artificial visual system (AVS), specifically incorporating mechanisms from horizontal and bipolar cells. This enhancement enables the model to proficiently identify object motion directions in grayscale images, aligning its threshold with human-like perception. The enhanced model demonstrates superior efficiency in motion direction recognition, requiring less data (90% less than other deep models) and less time for training. Experimental findings highlight the model's remarkable robustness, indicating significant potential for real-world applications. The integration of bio-inspired features not only enhances performance but also opens avenues for further exploration in neural network research. Notably, the application of this model to realistic object recognition yields convincing accuracy at nearly 100%, underscoring its practical utility. [ABSTRACT FROM AUTHOR]

Age-related neuronal adaptations are known to help maintain function. This study aims to examine gross age-related in vivo retinal functional adaptations (using electroretinography) in young and middle aged C57BL/6J and Thy1-YFPh mice and to relate this to in vivo retinal structure (using optical coherence tomography). Electroretinography responses were generally larger in Thy1-YFPh mice than in C57BL/6J mice, with similar in vivo retinal layer thicknesses except for longer inner/outer photoreceptor segment in Thy1-YFPh mice. Relative to 3-month-old mice, 12-month-old mice showed reduced photoreceptor (C57BL/6J 84.0±2.5 %; Thy1-YFPh 80.2±5.2 %) and bipolar cell (C57BL/6J 75.6±2.3 %; Thy1-YFPh 68.1±5.5 %) function. There was relative preservation of ganglion cell function (C57BL/6J 79.7±3.7 %; Thy1-YFPh 91.7±5.0 %) with age, which was associated with increased b-wave (bipolar cell) sensitivities to light. Ganglion cell function was correlated with both b-wave amplitude and sensitivity. This study shows that there are normal age-related adaptations to preserve functional output. Different mouse strains may have varied age-related adaptation capacity and should be taken into consideration when examining age-related susceptibility to injury. • Photoreceptor and bipolar cell function decline in middle aged mice. • Compensatory increase in bipolar cell sensitivity to light occurs in 12-month-old mice. • Increase inner retinal gain (ganglion cell function) up to 12 months of age. • Age-related functional differences can differ in transgenic mice. [ABSTRACT FROM AUTHOR]

In retinitis pigmentosa (RP), rod and cone photoreceptors degenerate, depriving downstream neurons of light-sensitive input, leading to vision impairment or blindness. Although downstream neurons survive, some undergo morphological and physiological remodeling. Bipolar cells (BCs) link photoreceptors, which sense light, to retinal ganglion cells (RGCs), which send information to the brain. While photoreceptor loss disrupts input synapses to BCs, whether BC output synapses remodel has remained unknown. Here we report that synaptic output from BCs plummets in RP mouse models of both sexes owing to loss of voltage-gated Ca2+ channels. Remodeling reduces the reliability of synaptic output to repeated optogenetic stimuli, causing RGC firing to fail at high-stimulus frequencies. Fortunately, functional remodeling of BCs can be reversed by inhibiting the retinoic acid receptor (RAR). RAR inhibitors targeted to BCs present a new therapeutic opportunity for mitigating detrimental effects of remodeling on signals initiated either by surviving photoreceptors or by vision-restoring tools. [ABSTRACT FROM AUTHOR]

In most avian retinas, double cones (consisting of a principal and accessory member) outnumber other photoreceptor types and have been associated with various functions, such as encoding luminance, sensing polarized light, and magnetoreception. However, their down-stream circuitry is poorly understood, particularly across bird species. Analysing species differences is important to understand changes in circuitry driven by ecological adaptations. We compare the ultrastructure of double cones and their postsynaptic bipolar cells between a night-migratory European robin and non-migratory chicken. We discover four previously unidentified bipolar cell types in the European robin retina, including midget-like bipolar cells mainly connected to one principal member. A downstream ganglion cell reveals a complete midget-like circuit similar to a circuit in the peripheral primate retina. Additionally, we identify a selective circuit transmitting information from a specific subset of accessory members. Our data highlight species-specific differences in double cone to bipolar cell connectivity, potentially reflecting ecological adaptations. Volume electron microscopy of retinas from two birds living in different habitats sheds light on species-specific wiring differences of double cone contacting bipolar cells and identifies principal and accessory member specific downstream circuits. [ABSTRACT FROM AUTHOR]

Purpose: To study the inner and outer retinal functions using a full-field electroretinogram (ERG) before and after intravenous chemotherapy (IVC) in children with retinoblastoma (RB). Methods: Of the 11 eyes, seven had RB and four were normal. All children were examined under anesthesia using a handheld ERG machine with a standard protocol – light-adapted single-flash ERG (fERG), photopic single-flash 3.0- and 30-Hz flickers, and photopic negative response (PhNR) amplitudes at 72 ms (P72). The amplitudes and peak times were compared before and after IVC. Results: Post-chemotherapy tumor regressed in all seven eyes. Of the seven eyes, the fERG peak time (a-wave) was delayed in two eyes (29%), whereas the b-wave was delayed in six eyes (86%). The fERG amplitude height for a- and b-waves decreased in five eyes (71%) and six eyes (86%), respectively. In addition, photopic flicker 30-Hz b-wave peak time delayed in five eyes (71%), whereas the b-wave amplitude height decreased in six eyes (86%). Simultaneously, the P72 amplitude height decreased in six eyes (86%), whereas the P-ratio increased in all seven eyes (100%). In comparison, the ERG responses improved in three of the four contralateral normal eyes. Overall, the cone function improved in two eyes (29%), whereas cone bipolar cell and retinal ganglion cell (RGC) function improved in one eye (14%) each. Conclusion: Comparison of light-adapted ERG changes before and after IVC showed reduced amplitudes and delayed peak times for both a and b waveforms, as well as reduced PhNR amplitude attributable to bipolar and RGC injury. [ABSTRACT FROM AUTHOR]

This document is a journal article titled "Continuing Professional Development" from the Clinical & Experimental Ophthalmology journal. It provides information on two articles included in the issue and presents multiple-choice questions related to the articles. The first article discusses the retention time of different ophthalmic viscosurgical devices during phacoemulsification in a rabbit ocular model. The second article evaluates keratometry and corneal astigmatism data from biometers and anterior segment tomographers and maps them to reconstructed corneal astigmatism. Another article in the journal discusses the natural history and biomarkers of KCNV2-associated retinopathy, while the last article explores the potential use of lipids from ocular meibum and tears as biomarkers for depression and post-traumatic stress disorder. The questions provided in the document test the reader's understanding of the articles' content. [Extracted from the article]

The spindle assembly checkpoint (SAC) temporally regulates mitosis by preventing progression from metaphase to anaphase until all chromosomes are correctly attached to the mitotic spindle. Centrosomes refine the spatial organization of the mitotic spindle at the spindle poles. However, centrosome loss leads to elongated mitosis, suggesting that centrosomes also inform the temporal organization of mitosis in mammalian cells. Here, we find that the mitotic delay in acentrosomal cells is enforced by the SAC in a MPS1-dependent manner, and that a SAC-dependent mitotic delay is required for bipolar cell division to occur in acentrosomal cells. Although acentrosomal cells become polyploid, polyploidy is not sufficient to cause dependency on a SAC-mediated delay to complete cell division. Rather, the division failure in absence of MPS1 activity results from mitotic exit occurring before acentrosomal spindles can become bipolar. Furthermore, prevention of centrosome separation suffices to make cell division reliant on a SAC-dependent mitotic delay. Thus, centrosomes and their definition of two spindle poles early in mitosis provide a 'timely two-ness' that allows cell division to occur in absence of a SAC-dependent mitotic delay. [ABSTRACT FROM AUTHOR]

Visual processing in the retina depends on the collective activity of large ensembles of neurons organized in different layers. Current techniques for measuring activity of layer-specific neural ensembles rely on expensive pulsed infrared lasers to drive 2-photon activation of calcium-dependent fluorescent reporters. We present a 1-photon light-sheet imaging system that can measure the activity in hundreds of neurons in the ex vivo retina over a large field of view while presenting visual stimuli. This allows for a reliable functional classification of different retinal cell types. We also demonstrate that the system has sufficient resolution to image calcium entry at individual synaptic release sites across the axon terminals of dozens of simultaneously imaged bipolar cells. The simple design, large field of view, and fast image acquisition make this a powerful system for high-throughput and high-resolution measurements of retinal processing at a fraction of the cost of alternative approaches.

The fovea of the human retina, a specialization for acute and color vision, features a high concentration of cone photoreceptors. A pit on the inner retinal aspect is created by the centrifugal migration of post-receptoral neurons. Foveal cells are specified early in fetal life, but the fovea reaches its final configuration postnatally. Pre-term birth retards migration resulting in a small pit, a small avascular zone, and nearly continuous inner retinal layers. To explore the involvement of Müller glia, we used serial-section electron microscopic reconstructions to examine the morphology and neural contacts of Müller glia contacting a single foveal cone in a 28-year-old male organ donor born at 28 weeks of gestation. A small nondescript foveal avascular zone contained massed glial processes that included a novel class of 'inner' Müller glia. Similar to classic 'outer' Müller glia that span the retina, inner Müller glia have bodies in the inner nuclear layer (INL). These cells are densely packed with intermediate filaments and insert processes between neurons. Unlike 'outer' Müller glia, 'inner' Müller glia do not reach the external limiting membrane but instead terminate at the outer plexiform layer. One completely reconstructed inner cell ensheathed cone pedicles and a cone-driven circuit of midget bipolar and ganglion cells. Inner Müller glia outnumber foveal cones by 1.8-fold in the outer nuclear layer (221,448 vs. 123,026 cells/mm²). Cell bodies of inner Müller glia outnumber those of outer Müller glia by 1.7-fold in the INL (41,872 vs. 24,631 cells/ mm²). Müller glia account for 95 and 80% of the volume of the foveal floor and Henle fiber layer, respectively. Determining whether inner cells are anomalies solely resulting from retarded lateral migration of inner retinal neurons in pre-term birth requires further research. [ABSTRACT FROM AUTHOR]

The number of vision sensors continues to increase with the rapid development of intelligent systems. The effective transmitting and processing of the sensing data become difficult due to the sensing, computing and memory units being physically separated. In-sensor computing architecture inspired by biological visual systems with efficient information processing has attracted increasing attention for overcoming these performance limitations. Bipolar cells in the retina can generate ON/OFF information processing channels to amplify marginal information. The synaptic structure is plastic and can enhance the output information that is repeated many times. In recent years, numerous new material and device strategies to implement in-sensor computing by mimicking the functions of bipolar cells and synapses have been reported: ON/OFF optical responses have been realized on two-dimensional materials by band-modulation and tunneling; synaptic responses, such as short-term plasticity and long-term plasticity, have been realized by phase transition and carrier regulating. In this review, we will summarize the biological vision processes, analyse the physical mechanisms behind the in-sensor computational vision sensors (ICVSs), and then overview the emerging physical artificial neural networks implemented with ICVSs. After that, we will discuss ICVS design based on biological mechanisms beyond ON/OFF bipolar-cell-response and synaptic response. [ABSTRACT FROM AUTHOR]

The thermal properties of bipolar plates, being key elements of polymer electrolyte membrane fuel cells, significantly affect their heat conduction and management. This study employed an innovative approach known as a heat flow loop integral method to experimentally assess the in-plane thermal conductivity of graphite bipolar plates, addressing the constraints of traditional methods that have strict demands for thermal stimulation, boundary or initial conditions, and sample size. This method employs infrared thermal imaging to gather information from the surface temperature field of the sample, which is induced by laser stimulation. An enclosed test loop on the infrared image of the sample's surface, situated between the heat source and the sample's boundary, is utilized to calculate the in-plane heat flow density by integrating the temperature at the sampling locations on the loop and the in-plane thermal conductivity can be determined based on Fourier's law of heat conduction. The numerical simulation analysis of the graphite models and the experimental tests with aluminum have confirmed the precision and practicality of this method. The results of 1060 aluminum and 6061 aluminum samples, each 1 and 2 mm in thickness, show a deviation between the reference and actual measurements of the in-plane thermal conductivity within 4.3% and repeatability within 2.7%. Using the loop integral method, the in-plane thermal conductivities of three graphite bipolar plates with thicknesses of 0.5 mm, 1 mm, and 1.5 mm were tested, resulting in 311.98 W(m·K)−1, 314.41 W(m·K)−1, and 323.48 W(m·K)−1, with repeatabilities of 0.9%, 3.0%, and 2.0%, respectively. A comparison with the reference value from the simulation model for graphite bipolar plates with the same thickness showed a deviation of 4.7%. The test results for three different thicknesses of graphite bipolar plates show a repeatability of 2.6%, indicating the high consistency and reliability of this measurement method. Consequently, as a supplement to existing technology, this method can achieve a rapid and nondestructive measurement of materials such as graphite bipolar plates' in-plane thermal conductivity. [ABSTRACT FROM AUTHOR]

Vertebrate vision begins with light absorption by rod and cone photoreceptors, which transmit signals from their synaptic terminals to second-order neurons: bipolar and horizontal cells. In mouse rods, there is a single presynaptic ribbon-type active zone at which the release of glutamate occurs tonically in the dark. This tonic glutamatergic signaling requires continuous exo- and endocytosis of synaptic vesicles. At conventional synapses, endocytosis commonly requires dynamins: GTPases encoded by three genes (Dnm1-3), which perform membrane scission. Disrupting endocytosis by dynamin deletions impairs transmission at conventional synapses, but the impact of disrupting endocytosis and the role(s) of specific dynamin isoforms at rod ribbon synapses are understood incompletely. Here, we used cell-specific knock-outs (KOs) of the neuron-specific Dnm1 and Dnm3 to investigate the functional roles of dynamin isoforms in rod photoreceptors in mice of either sex. Analysis of synaptic protein expression, synapse ultrastructure, and retinal function via electroretinograms (ERGs) showed that dynamins 1 and 3 act redundantly and are essential for supporting the structural and functional integrity of rod ribbon synapses. Single Dnm3 KO showed no phenotype, and single Dnm1 KO only modestly reduced synaptic vesicle density without affecting vesicle size and overall synapse integrity, whereas double Dnm1/Dnm3 KO impaired vesicle endocytosis profoundly, causing enlarged vesicles, reduced vesicle density, reduced ERG responses, synaptic terminal degeneration, and disassembly and degeneration of postsynaptic processes. Concurrently, cone function remained intact. These results show the fundamental redundancy of dynamins 1 and 3 in regulating the structure and function of rod ribbon synapses. [ABSTRACT FROM AUTHOR]

Introduction: Mechanical sensitive channels expressed in mammalian retinas are effectors of elevated pressure stresses, but it is unclear how their activation affects visual function in pressure-related retinal disorders. Methods: This study investigated the role of the transient potential channel vanilloid TRPV4 in photoreceptors and rod bipolar cells (RBCs) with immunohistochemistry, confocal microscopy, electroretinography (ERG), and patch-clamp techniques. Results: TRPV4 immunoreactivity (IR) was found in the outer segments of photoreceptors, dendrites and somas of PKCa-positive RBCs and other BCs, plexiform layers, and retinal ganglion cells (RGCs) in wild-type mice. TRPV4-IR was largely diminished in the retinas of homozygous TRPV4 transgenic mice. Genetically suppressing TRPV4 expression moderately but significantly enhanced the amplitude of ERG a- and b-waves evoked by scotopic and mesopic lights (0.55 to 200 Rh*rod-1 s-1) and photopic lights (105-106 Rh*rod-1 s-1) compared to wildtype mice in fully dark-adapted conditions. The implicit time evoked by dim lights (0.55 to 200 Rh*rod-1 s-1) was significantly decreased for b-waves and elongated for a-waves in the transgenic mice. ERG b-wave evoked by dim lights is primarily mediated by RBCs, and under voltage-clamp conditions, the latency of the lightevoked cation current in RBCs of the transgenic mice was significantly shorter compared to wild-type mice. About 10% of the transgenic mice had one eye undeveloped, and the percentage was significantly higher than in wild-type mice. Conclusions: The data indicates that TRPV4 involves ocular development and is expressed and active in outer retinal neurons, and interventions of TRPV4 can variably affect visual signals in rods, cones, RBCs, and cone ON BCs. [ABSTRACT FROM AUTHOR]

Immune imbalances are associated with the pathogenesis and pharmacological efficacy of bipolar disorder (BD). The underlying mechanisms remain largely obscure but may involve immunometabolic dysfunctions of T-lymphocytes. We investigated if inflammatory cytokines and the immunometabolic function of T-lymphocytes, including frequencies of subsets, mitochondrial mass (MM), and low mitochondrial membrane potential (MMPLow) differed between BD patients (n = 47) and healthy controls (HC, n = 43). During lithium treatment of hospitalized patients (n = 33), the association between weekly T-lymphocyte immune metabolism and clinical symptoms was analyzed, and preliminary explorations on possible mechanisms were conducted. In comparison to HC, BD patients predominantly showed a trend toward CD4+ naïve T (Tn) activation and exhibited mitochondrial metabolic disturbances such as decreased MM and increased MMPLow. Lower CD4+ Tn-MM correlated with elevated IL-6, IL-8, and decreased IL-17 A in BD patients. With lithium treatment effective, MM of CD4+ T/Tn was negatively correlated with depression score HAMD. When lithium intolerance was present, MM of CD4+ T/Tn was positively correlated with depression score HAMD and mania score BRMS. Lithium does not mediate through the inositol depletion hypothesis, but the mRNA level of IMPA2 in peripheral blood is associated with mitochondrial function in CD8+ T cells. The cross-sectional design and short-term follow-up meant that we could not directly examine the causality of BD and immune dysregulation. The altered metabolism of CD4+ Tn was strongly associated with remodeling of the inflammatory landscape in BD patients and can also be used to reflect the short-term therapeutic effects of lithium. [Display omitted] • Activation of circulating CD4+ naive T cells is observed in BD patients. • Lower mitochondrial mass of CD4+ naive T is a pivotal mediator mediating immune dysfunction in BD patients. • Enhancing the mitochondrial mass of naïve T-cells might be a potential therapeutic target for BD. • The emergence of drug intolerance disrupts the immunomodulatory effects of lithium on T-cells. [ABSTRACT FROM AUTHOR]

Understanding how different neuronal types connect and communicate is critical to interpreting brain function and behavior. However, it has remained a formidable challenge to decipher the genetic underpinnings that dictate the specific connections formed between neuronal types. To address this, we propose a novel bilinear modeling approach that leverages the architecture similar to that of recommendation systems. Our model transforms the gene expressions of presynaptic and postsynaptic neuronal types, obtained from single-cell transcriptomics, into a covariance matrix. The objective is to construct this covariance matrix that closely mirrors a connectivity matrix, derived from connectomic data, reflecting the known anatomical connections between these neuronal types. When tested on a dataset of Caenorhabditis elegans, our model achieved a performance comparable to, if slightly better than, the previously proposed spatial connectome model (SCM) in reconstructing electrical synaptic connectivity based on gene expressions. Through a comparative analysis, our model not only captured all genetic interactions identified by the SCM but also inferred additional ones. Applied to a mouse retinal neuronal dataset, the bilinear model successfully recapitulated recognized connectivity motifs between bipolar cells and retinal ganglion cells, and provided interpretable insights into genetic interactions shaping the connectivity. Specifically, it identified unique genetic signatures associated with different connectivity motifs, including genes important to cell-cell adhesion and synapse formation, highlighting their role in orchestrating specific synaptic connections between these neurons. Our work establishes an innovative computational strategy for decoding the genetic programming of neuronal type connectivity. It not only sets a new benchmark for single-cell transcriptomic analysis of synaptic connections but also paves the way for mechanistic studies of neural circuit assembly and genetic manipulation of circuit wiring. [ABSTRACT FROM AUTHOR]

We consider a model of basic inner retinal connectivity where bipolar and amacrine cells interconnect and both cell types project onto ganglion cells, modulating their response output to the brain visual areas. We derive an analytical formula for the spatiotemporal response of retinal ganglion cells to stimuli, taking into account the effects of amacrine cells inhibition. This analysis reveals two important functional parameters of the network: (1) the intensity of the interactions between bipolar and amacrine cells and (2) the characteristic timescale of these responses. Both parameters have a profound combined impact on the spatiotemporal features of retinal ganglion cells' responses to light. The validity of the model is confirmed by faithfully reproducing pharmacogenetic experimental results obtained by stimulating excitatory DREADDs (Designer Receptors Exclusively Activated by Designer Drugs) expressed on ganglion cells and amacrine cells' subclasses, thereby modifying the inner retinal network activity to visual stimuli in a complex, entangled manner. Our mathematical model allows us to explore and decipher these complex effects in a manner that would not be feasible experimentally and provides novel insights in retinal dynamics. [ABSTRACT FROM AUTHOR]

The complex nature of the retina demands well-organized signaling to uphold signal accuracy and avoid interference, a critical aspect in handling a variety of visual stimuli. A-kinase anchoring proteins (AKAPs), known for binding protein kinase A (PKA), contribute to the specificity and efficiency of retinal signaling. They play multifaceted roles in various retinal cell types, influencing photoreceptor sensitivity, neurotransmitter release in bipolar cells, and the integration of visual information in ganglion cells. AKAPs like AKAP79/150 and AKAP95 exhibit distinct subcellular localizations, impacting synaptic transmission and receptor sensitivity in photoreceptors and bipolar cells. Furthermore, AKAPs are involved in neuroprotective mechanisms and axonal degeneration, particularly in retinal ganglion cells. In particular, AKAP6 coordinates stressspecific signaling and promotes neuroprotection following optic nerve injury. As our review underscores the therapeutic potential of targeting AKAP signaling complexes for retinal neuroprotection and enhancement, it acknowledges challenges in developing selective drugs that target complex protein--protein interactions. Overall, this exploration of AKAPs provides valuable insights into the intricacies of retinal signaling, offering a foundation for understanding and potentially addressing retinal disorders. [ABSTRACT FROM AUTHOR]

The ambient daylight variation is coded by melanopsin photoreceptors and their luxotonic activity increases towards midday when colour temperatures are cooler, and irradiances are higher. Although melanopsin and cone photoresponses can be mediated via separate pathways, the connectivity of melanopsin cells across all levels of the retina enables them to modify cone signals. The downstream effects of melanopsin-cone interactions on human vision are however, incompletely understood. Here, we determined how the change in daytime melanopsin activation affects the human cone pathway signals in the visual cortex. A 5-primary silent-substitution method was developed to evaluate the dependence of cone-mediated signals on melanopsin activation by spectrally tuning the lights and stabilizing the rhodopsin activation under a constant cone photometric luminance. The retinal (white noise electroretinogram) and cortical responses (visual evoked potential) were simultaneously recorded with the photoreceptor-directed lights in 10 observers. By increasing the melanopsin activation, a reverse response pattern was observed with cone signals being supressed in the retina by 27% (p = 0.03) and subsequently amplified by 16% (p = 0.01) as they reach the cortex. We infer that melanopsin activity can amplify cone signals at sites distal to retinal bipolar cells to cause a decrease in the psychophysical Weber fraction for cone vision. [ABSTRACT FROM AUTHOR]

Alterations in intraocular and external pressure critically involve the pathogenesis of glaucoma, traumatic retinal injury (TRI), and other retinal disorders, and retinal neurons have been reported to express multiple mechanical-sensitive channels (MSCs) in recent decades. However, the role of MSCs in visual functions and pressure-related retinal conditions has been unclear. This review will focus on the variety and functional significance of the MSCs permeable to K+, Na+, and Ca2+, primarily including the big potassium channel (BK); the two-pore domain potassium channels TRAAK and TREK; Piezo; the epithelial sodium channel (ENaC); and the transient receptor potential channels vanilloid TRPV1, TRPV2, and TRPV4 in retinal photoreceptors, bipolar cells, horizontal cells, amacrine cells, and ganglion cells. Most MSCs do not directly mediate visual signals in vertebrate retinas. On the other hand, some studies have shown that MSCs can open in physiological conditions and regulate the activities of retinal neurons. While these data reasonably predict the crossing of visual and mechanical signals, how retinal light pathways deal with endogenous and exogenous mechanical stimulation is uncertain. [ABSTRACT FROM AUTHOR]

Summary: Sperm development and structure in the wood-inhabiting fungal and plant-feeding nematode, Bursaphelenchus luxuriosae , were studied using transmission electron microscopy to evaluate interspecific similarities and differences of spermatozoa in nematodes. In general, spermatogenesis in B. luxuriosae fits the 'rhabditid' pattern supported by morphological and phylogenetic analysis of the order Rhabditida. Spermatocyte development includes formation of complexes of fibrous bodies (FBs) with membranous organelles (MOs), the complexes dissociate in the spermatids into separate components, and the immature sperm contain MOs but lack FBs, which transform into a dense matrix of sperm cytoplasm. The female spermatheca contains mature spermatozoa as bipolar cells subdivided into a pseudopod devoid of organelles and a main cell body containing a nucleus without a nuclear envelope, numerous mitochondria, and peripheral MOs as pouches opening to the exterior via pores. Data on B. luxuriosae are used for analysis of variable quantitative and morphological characteristics of spermatozoa in Aphelenchoidea. General size of spermatozoa and their MOs have little value for comparative analysis. The MO knobbles look uniform in immature spermatozoa of each aphelenchoidid species studied and may be considered as a taxonomically specific ultrastructural feature. The presence or absence of FBs in immature spermatozoa demonstrates the diagnostic value of the aphelenchoidid sperm structure at the species level. Analysis also shows close similarity of spermatozoa in Bursaphelenchus spp. and Caenorhabditis elegans , the model species with comprehensive data on sperm biology. This may be used to identify new ways for the control and suppression of harmful nematode species such as B. xylophilus. [ABSTRACT FROM AUTHOR]

Melanoma-associated retinopathy (MAR) is a paraneoplastic syndrome associated with cutaneous metastatic melanoma in which patients develop vision deficits that include reduced night vision, poor contrast sensitivity, and photopsia. MAR is caused by autoantibodies targeting TRPM1, an ion channel found in melanocytes and retinal ON-bipolar cells (ON-BCs). The visual symptoms arise when TRPM1 autoantibodies enter ON-BCs and block the function of TRPM1, thus detection of TRPM1 autoantibodies in patient serum is a key criterion in diagnosing MAR. Electroretinograms are used to measure the impact of TRPM1 autoantibodies on ON-BC function and represent another important diagnostic tool for MAR. To date, MAR case reports have included one or both diagnostic components, but only for a single time point in the course of a patient’s disease. Here, we report a case of MAR supported by longitudinal analysis of serum autoantibody detection, visual function, ocular inflammation, vascular integrity, and response to slow-release intraocular corticosteroids. Integrating these data with the patient’s oncological and ophthalmological records reveals novel insights regarding MAR pathogenesis, progression, and treatment, which may inform new research and expand our collective understanding of the disease. In brief, we find TRPM1 autoantibodies can disrupt vision even when serum levels are barely detectable by western blot and immunohistochemistry; intraocular dexamethasone treatment alleviates MAR visual symptoms despite high levels of circulating TRPM1 autoantibodies, implicating antibody access to the retina as a key factor in MAR pathogenesis. Elevated inflammatory cytokine levels in the patient’s eyes may be responsible for the observed damage to the blood-retinal barrier and subsequent entry of autoantibodies into the retina.

PurposeLoss of retinoschisin (RS1) function underlies X-linked retinoschisis (XLRS) pathology. In the retina, both photoreceptor inner segments and bipolar cells express RS1. However, the loss of RS1 function causes schisis primarily in the inner retina. To understand these cell type-specific phenotypes, we decoupled RS1 effects in bipolar cells from that in photoreceptors.MethodsBipolar cell transgene RS1 expression was achieved using two inner retina-specific promoters: (1) a minimal promoter engineered from glutamate receptor, metabotropic glutamate receptor 6 gene (mini-mGluR6/ Grm6) and (2) MiniPromoter (Ple155). Adeno-associated virus vectors encoding RS1 gene under either the mini-mGluR6 or Ple-155 promoter were delivered to the XLRS mouse retina through intravitreal or subretinal injection on postnatal day 14. Retinal structure and function were assessed 5 weeks later: immunohistochemistry for morphological characterization, optical coherence tomography and electroretinography (ERG) for structural and functional evaluation.ResultsImmunohistochemical analysis of RS1expression showed that expression with the MiniPromoter (Ple155) was heavily enriched in bipolar cells. Despite variations in vector penetrance and gene transfer efficiency across the injected retinas, those retinal areas with robust bipolar cell RS1 expression showed tightly packed bipolar cells with fewer cavities and marked improvement in inner retinal structure and synaptic function as judged by optical coherence tomography and electroretinography, respectively.ConclusionsThese results demonstrate that RS1 gene expression primarily in bipolar cells of the XLRS mouse retina, independent of photoreceptor expression, can ameliorate retinoschisis structural pathology and provide further evidence of RS1 role in cell adhesion.

Photoreceptors are electrically coupled to one another, and the spatiotemporal properties of electrical synapses in a two-dimensional retinal network are still not well studied, because of the limitation of the single electrode or pair recording techniques which do not allow simultaneously measuring responses of multiple photoreceptors at various locations in the retina. A multiple electrode recording system is needed. In this study, we investigate the network properties of the two-dimensional rod coupled array of the salamander retina (both sexes were used) by using the newly available multiple patch electrode system that allows simultaneous recordings from up to eight cells and to determine the electrical connectivity among multiple rods. We found direct evidence that voltage signal spread in the rod-rod coupling network in the absence of Ih (mediated by HCN channels) is passive and follows the linear cable equation. Under physiological conditions, Ih shapes the network signal by progressively shortening the response time-to-peak of distant rods, compensating the time loss of signal traveling from distant rods to bipolar cell somas and facilitating synchronization of rod output signals. Under voltage-clamp conditions, current flow within the coupled rods follows Ohm's law, supporting the idea that nonlinear behaviors of the rod network are dependent on membrane voltage. Rod-rod coupling is largely symmetrical in the 2D array, and voltage-clamp blocking the next neighboring rod largely suppresses rod signal spread into the second neighboring rod, suggesting that indirect coupling pathways play a minor role in rod-rod coupling. [ABSTRACT FROM AUTHOR]

Degeneration of photoreceptors in the retina is a leading cause of blindness, but commonly leaves the retinal ganglion cells (RGCs) and/or bipolar cells extant. Consequently, these cells are an attractive target for the invasive electrical implants colloquially known as "bionic eyes." However, after more than two decades of concerted effort, interfaces based on conventional electrical stimulation approaches have delivered limited efficacy, primarily due to the current spread in retinal tissue, which precludes high-acuity vision. The ideal prosthetic solution would be less invasive, provide single-cell resolution and an ability to differentiate between different cell types. Nanoparticlemediated approaches can address some of these requirements, with particular attention being directed at light-sensitive nanoparticles that can be accessed via the intrinsic optics of the eye. Here we survey the available known nanoparticle-based optical transduction mechanisms that can be exploited for neuromodulation. We review the rapid progress in the field, together with outstanding challenges that must be addressed to translate these techniques to clinical practice. In particular, successful translation will likely require efficient delivery of nanoparticles to stable and precisely defined locations in the retinal tissues. Therefore, we also emphasize the current literature relating to the pharmacokinetics of nanoparticles in the eye. While considerable challenges remain to be overcome, progress to date shows great potential for nanoparticlebased interfaces to revolutionize the field of visual prostheses. [ABSTRACT FROM AUTHOR]

Retinal bipolar and amacrine cells receive visual information from photoreceptors and participate in the first steps of image processing in the retina. Several studies have suggested the operation of aerobic glycolysis and a lactate shuttle system in the retina due to the high production of this metabolite under aerobic conditions. However, whether bipolar cells form part of this metabolic circuit remains unclear. Here, we show that the monocarboxylate transporter 2 is expressed and functional in inner retinal neurons. Additionally, we used genetically encoded FRET nanosensors to demonstrate the ability of inner retinal neurons to consume extracellular lactate as an alternative to glucose. In rod bipolar cells, lactate consumption allowed cells to maintain the homeostasis of ions and electrical responses. We also found that lactate synthesis and transporter inhibition caused functional alterations and an increased rate of cell death. Overall, our data shed light on a notable but still poorly understood aspect of retinal metabolism. [ABSTRACT FROM AUTHOR]

Synaptic transmission from retinal photoreceptors to downstream ON-type bipolar cells (BCs) depends on the postsynaptic metabotropic glutamate receptor mGluR6, located at the BC dendritic tips. Glutamate binding to mGluR6 initiates G-protein signaling that ultimately leads to BC depolarization in response to light. The mGluR6 receptor also engages in trans-synaptic interactions with presynaptic ELFN adhesion proteins. The roles of post-translational modifications in mGluR6 trafficking and function are unknown. Treatment with glycosidase enzymes PNGase F and Endo H demonstrated that both endogenous and heterologously expressed mGluR6 contain complex N-glycosylation acquired in the Golgi. Pull-down experiments with ELFN1 and ELFN2 extracellular domains revealed that these proteins interact exclusively with the complex glycosylated form of mGluR6. Mutation of the four predicted N-glycosylation sites, either singly or in combination, revealed that all four sites are glycosylated. Single mutations partially reduced, but did not abolish, surface expression in heterologous cells, while triple mutants had little or no surface expression, indicating that no single glycosylation site is necessary or sufficient for plasma membrane trafficking. Mutation at N445 severely impaired both ELFN1 and ELFN2 binding. All single mutants exhibited dendritic tip enrichment in rod BCs, as did the triple mutant with N445 as the sole N-glycosylation site, demonstrating that glycosylation at N445 is sufficient but not necessary for dendritic tip localization. The quadruple mutant was completely mislocalized. These results reveal a key role for complex Nglycosylation in regulating mGluR6 trafficking and ELFN binding, and by extension, function of the photoreceptor synapses. [ABSTRACT FROM AUTHOR]

The microanatomy of the donkey eye is important to understand because pathological disorders affecting them are relatively common. The current study aimed to document the cellular components of donkey's retinae using light and electron microscopic studies. Ten donkey retinae were dissected and processed for semi-thin sections and electron microscopic studies. The photoreceptor layer was made up of the outer and inner segments of rods and cones. The outer segments were filled with invaginations of cell membranes that form stacks of membranous disks. Shed discs of photoreceptor outer segments could be seen in the photoreceptor layer as well as near the Müller cells. The inner segments of cones were conical in shape, while those of rods were slim rod-shaped. Both were filled with long thin mitochondria and free ribosomes. Three rows of photoreceptor cell nuclei made up the outer nuclear layer. The rod nuclei had more electron-dense chromatin than those of the cones. There were two rows of cell nuclei in the inner nuclear layer that represent the following four cell classes: horizontal cells, bipolar cells, amacrine cells, and Müller cells. Bipolar cells constitute the bulk of the inner nuclear layer. They were elongated in shape and had thick branched dendrites. Amacrine cells were in the inner face of the INL. It could be observed within IPL and known as displaced amacrine cells. Muller glial cells were irregular elongated in shape with many cytoplasmic processes. They were distributed in the INL among the bipolar cells. Müller cells were observed in the inner plexiform layer, the ganglion cell layer, and the nerve fiber layer. In conclusion, this study characterized the detailed cytological organization and ultrastructure of the healthy donkey retina. which maintains the fundamental laminar architecture characteristic of other mammalian retinas, and consists of 10 distinguishable layers. When compared to previously described retinal morphologies in domestic species, some distinctive characters were observed in donkey retinal cells. [ABSTRACT FROM AUTHOR]

Simple Summary: This study scrutinized the retinal composition of Molly fish (Poecilia sphenops), revealing a complex neuronal structure. The retina showcased a distinctive square mosaic layout of cones, incorporating double cones alongside two variants of single cones. Within the inner nuclear layer, a diverse array of cells and Müller cell processes, expressing GFAP, traversed the retina. Notably, astrocyte cell processes expressing GFAP were discernible in both the inner and outer plexiform layers. Overall, Molly fish's retina displayed a sophisticated structure characterized by a high density of photoreceptors, bipolar, amacrine, horizontal, Müller cells, and astrocytes, suggesting robust photopic visual capabilities. The specific arrangement and distribution of photoreceptors in the retina can vary among different fish species, with each species exhibiting adaptations related to its habitat, behavior, and visual requirements. Poecilia sphenops, a diurnal fish, was the focus of this study. The retinas of a total of eighteen Molly fish were investigated utilizing light and electron microscopy. The retina exhibited a square mosaic pattern of the inner segments of cones. This pattern comprised double cones positioned along the sides of a square, with two types of single cones situated at the center and corners of the square arrangement across the entire retina. The corner cones were slightly shorter than the central ones. Additionally, the outer plexiform layer contained both cone pedicles and rod spherules. The rod spherule consisted of a single synaptic ribbon arranged in a triad or quadrat junctional arrangement within the invaginating free ends of the horizontal and bipolar cell processes. On the other hand, cone pedicles have more than one synaptic ribbon in their junctional complex. The inner nuclear layer consisted of the amacrine, bipolar, Müller, and horizontal cell bodies. Müller cell processes, expressing GFAP, extended across all retinal layers, segmenting the deeper retina into alternating fascicles of optic axons and ganglion cells. The outer and inner plexiform layers showed many astrocyte cell processes expressing GFAP. In conclusion, the current study is the first record of the retinal structures of Molly fish. This study illustrated the mosaic arrangement of photoreceptors and GFAP expression patterns of astrocytes and Müller cells. The presence of three cone types, coupled with a sufficient number of rods, likely facilitates motion awareness for tasks like finding food and performing elaborate mating ceremonies. [ABSTRACT FROM AUTHOR]

Titanium has a low density and high corrosion resistance. In order to achieve the goal of a lightweight material, and to extend the normal working hour of proton-exchange membrane fuel cells (PEMFCs), ultra-thin titanium plates were chosen to manufacture the key components—bipolar plates (BPs). For the purpose of overcoming the challenges of manufacturing with a large depth to width ratio, a multi-stage formation process was established with characteristics such as high efficiency and a lower price. In this study, the process parameters were examined through an experimental approach. The outcomes show that the channel formed by multistage forming is deeper than that formed by single-stage forming under the same displacement conditions. To achieve greater flow depths, it is recommended to increase the displacements as much as possible during both the first- and second-stage forming processes. The implementation of three-stage forming can effectively reduce the maximum thinning rates within flow channels while improving the overall deformation uniformity. This method deviates from traditional one-stage loading processes by adopting multi-stage loading instead. By employing appropriate mold designs, material deformation and flow can be enhanced throughout gradual loading processes, thereby preventing strain concentration and enhancing the ultimate formation height accuracy within micro-flow channels. Consequently, the proposed three-stage forming process proves highly appropriate for the mass production of BPs utilizing titanium plates. [ABSTRACT FROM AUTHOR]