{"title":"Immunosuppressant-free photosensitivity rescue of mnu-injured mice using human photoreceptor-like cells induced by rapid chemical reprogramming of fibroblasts as an intermediate stage","authors":"Zhe Xu, Yuan Liang, Sensen Zhang, Yuanyue Liu, Sen-Ning Liu, Siting Liang, Zhiyuan Li, Tian Guan, Ying Xu, Haoyu Zeng","doi":"10.48130/vns-0025-0003","DOIUrl":"https://doi.org/10.48130/vns-0025-0003","url":null,"abstract":"Recent studies have revealed that photoreceptor-like cells derived from human induced pluripotent stem-cells (hiPSCs) were a potential approach for reversing lost vision. To make the hiPSC application in a clinical setting more accessible and efficient, we have developed a two-step method to differentiate an adequate number of chemically-induced photoreceptor-like cells (CiPCs) cells from hiPSCs in a shorter period (three weeks) through chemical reprogramming. The CiPCs were verified through cell morphology and flow cytometry methods for the expression of photoreceptor markers. The electrical signal detection of calcium, potassium, and sodium channels was performed with an <italic>in vitro</italic> model to determine the function of CiPCs. ERG recording was utilized for the <italic>in vivo</italic> evaluation. Photoreceptor markers, including recoverin and rhodopsin, were expressed in the CiPCs. Calcium, potassium, and sodium signals were detected in CiPCs. Clear ERG responses were observed in the retina of four out of six CiPCs transplanted mice (MNU-injured model), while none was observed in the control group. Moreover, classic symptoms of immune rejection were unobserved in the eyes of mice. Consequently, our hiPSC-derived photoreceptor-like cells successfully restored photosensitivity in photoreceptor-degenerated mice, indicating a potential clinical application for etiologically treating retinal degenerative diseases and restoring lost vision with less, or even no need for immunosuppressants.","PeriodicalId":23556,"journal":{"name":"Visual Neuroscience","volume":"42 1","pages":"0-0"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147331297","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Microglial phagocytosis involves hyperoxia-induced vessel regression in the neonatal retina","authors":"Zhuojun Xu, Yuan Ma, Jionghao Li, Jiejie Zhuang, Yaping Liu, Zhuangling Lin, Baoyi Liu, Zhuoting Zhu, Ziye Chen, Xiaoyue Wei, Lan Jiang, Rebiya Tuxun, Zitong Chen, Chin-Ling Tsai, Jing Zhuang, Tao Li","doi":"10.48130/vns-0025-0004","DOIUrl":"https://doi.org/10.48130/vns-0025-0004","url":null,"abstract":"Oxygen concentration fluctuations are fundamental contributors to retinopathy of prematurity and other retinal neovascular diseases. However, the mechanism of retinal vascular regression under high oxygen stimulation remains unclear. In this study, we employed an oxygen-induced retinopathy mouse model to investigate the role of microglia in hyperoxia-induced vessel regression. Retinal vascular regression characteristics, microglial morphology, and localization were observed using immunofluorescence staining. Expression levels of phagocytic-related factors were analyzed via qPCR and Western blot techniques. Additionally, microglia were partially depleted to verify their functional contributions. TUNEL assay and RNA sequencing were performed to further explore the underlying mechanisms. Our findings indicated that central retinal vascular regression occurs rapidly at an early stage, accompanied by microglial migration and activation. Endothelial cell fragments were detected within microglia, confirming their involvement with phagocytic function, the upregulation of phagocytic-related factors further proved it. Notably, partial depletion of microglia significantly inhibited early retinal vascular regression and reduced endothelial cell apoptosis. Moreover, RNA sequencing and bioinformatics analysis revealed that microglial phagocytosis is regulated by the complement pathway. In conclusion, our study confirms the active participation of microglia in hyperoxia-induced retinal vascular regression through phagocytosis, thereby providing potential targets for early intervention in related diseases.","PeriodicalId":23556,"journal":{"name":"Visual Neuroscience","volume":"42 1","pages":"0-0"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147904493","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lu Cheng, Xiaoxin Liu, Kangjia Lv, Yu‐Chen Zhang, Peiyao Jin, Tianwei Qian, Jin Wei, Yali Zhou, Fudong Yu, Junwei Fang, Chong Chen, Kun Liu, Xun Xu
{"title":"Neuropeptide VF promotes hypoxia-inducible factor-1<b><i>α</i></b> expression in age-related macular degeneration via the aldehyde dehydrogenase 2/D-glycerate axis","authors":"Lu Cheng, Xiaoxin Liu, Kangjia Lv, Yu‐Chen Zhang, Peiyao Jin, Tianwei Qian, Jin Wei, Yali Zhou, Fudong Yu, Junwei Fang, Chong Chen, Kun Liu, Xun Xu","doi":"10.48130/vns-0025-0023","DOIUrl":"https://doi.org/10.48130/vns-0025-0023","url":null,"abstract":"Age-related macular degeneration (AMD) is the leading cause of blindness; however, its underlying pathogenesis remains unclear. This study investigated the role of the neuropeptide VF (NPVF) in AMD. Transcriptome profiling in retinal-choroid tissues was analyzed using a public dataset. There was an increase in NPVF expression in the retinal-choroid tissues of eyes with AMD, which was more significant in wet AMD. Serological validation was conducted to verify the expression of NPVF in 30 wet AMD patients and 30 controls, and a statistically significant increase in serum NPVF concentration was observed in wet AMD patients. The role of NPVF in AMD was then investigated through <italic>in vitro</italic> experiments involving the overexpression of NPVF in a human retinal pigment epithelium (RPE) cell line. Overexpression of NPVF resulted in a marked upregulation of hypoxia-inducible factor-1<italic>α</italic> (HIF-1<italic>α</italic>), a key regulator implicated in the pathogenesis of AMD and associated neovascularization, and further promotes the secretion of vascular endothelial growth factor and enhances endothelial tube formation. By integrating transcriptomic and metabolomic data, it was found that aldehyde dehydrogenase 2 (ALDH2) was upregulated, whereas its substrate, D-glycerate, was downregulated in NPVF-overexpressing RPE cells. Further experimental validation confirmed that NPVF regulates HIF-1<italic>α</italic> expression through the ALDH2/D-glycerate axis. In summary, the present findings suggest that NPVF contributes to AMD pathogenesis via the ALDH2/D-glycerate/HIF-1<italic>α</italic> pathway.","PeriodicalId":23556,"journal":{"name":"Visual Neuroscience","volume":"42 1","pages":"0-0"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.maxapress.com/data/article/opr/preview/pdf/vns-0025-0023.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147913318","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Support for the efficient coding account of visual discomfort.","authors":"Louise O'Hare, Paul B Hibbard","doi":"10.1017/S0952523824000051","DOIUrl":"10.1017/S0952523824000051","url":null,"abstract":"<p><p>Sparse coding theories suggest that the visual brain is optimized to encode natural visual stimuli to minimize metabolic cost. It is thought that images that do not have the same statistical properties as natural images are unable to be coded efficiently and result in visual discomfort. Conversely, artworks are thought to be even more efficiently processed compared to natural images and so are esthetically pleasing. This project investigated visual discomfort in uncomfortable images, natural scenes, and artworks using a combination of low-level image statistical analysis, mathematical modeling, and EEG measures. Results showed that the model response predicted discomfort judgments. Moreover, low-level image statistics including edge predictability predict discomfort judgments, whereas contrast information predicts the steady-state visually evoked potential responses. In conclusion, this study demonstrates that discomfort judgments for a wide set of images can be influenced by contrast and edge information, and can be predicted by our models of low-level vision, whilst neural responses are more defined by contrast-based metrics, when contrast is allowed to vary.</p>","PeriodicalId":23556,"journal":{"name":"Visual Neuroscience","volume":"41 ","pages":"E008"},"PeriodicalIF":1.1,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11730975/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142898463","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Martin Timothy Wilkinson Scott, Alexandra Yakovleva, Anthony Matthew Norcia
{"title":"Visual Field Asymmetries in Responses to ON and OFF Pathway Biasing Stimuli.","authors":"Martin Timothy Wilkinson Scott, Alexandra Yakovleva, Anthony Matthew Norcia","doi":"10.1017/S095252382400004X","DOIUrl":"10.1017/S095252382400004X","url":null,"abstract":"<p><p>Recent reports suggest the ON and OFF pathways are differentially susceptible to selective vision loss in glaucoma. Thus, perimetric assessment of ON- and OFF-pathway function may serve as a useful diagnostic. However, this necessitates a developed understanding of normal ON/OFF pathway function around the visual field and as a function of input intensity. Here, using electroencephalography, we measured ON- and OFF-pathway biased contrast response functions in the upper and lower visual fields. Using the steady-state visually evoked potential paradigm, we flickered achromatic luminance probes according to a saw-tooth waveform, the fast phase of which biased responses towards the ON or OFF pathways. Neural responses from the upper and lower visual fields were simultaneously measured using frequency tagging - probes in the upper visual field modulated at 3.75 Hz, while those in the lower visual field modulated at 3 Hz. We find that responses to OFF/decrements are larger than ON/increments, especially in the lower visual field. In the lower visual field, both ON and OFF responses were well described by a sigmoidal non-linearity. In the upper visual field, the ON pathway function was very similar to that of the lower, but the OFF pathway function showed reduced saturation and more cross-subject variability. Overall, this demonstrates that the relationship between the ON and OFF pathways depends on the visual field location and contrast level, potentially reflective of natural scene statistics.</p>","PeriodicalId":23556,"journal":{"name":"Visual Neuroscience","volume":"41 ","pages":"E007"},"PeriodicalIF":1.1,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11730990/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142855612","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Christabel Arthur, Osman B Kavcar, Mackenzie V Wise, Michael A Crognale
{"title":"Pattern reversal chromatic VEPs like onsets, are unaffected by attentional demand.","authors":"Christabel Arthur, Osman B Kavcar, Mackenzie V Wise, Michael A Crognale","doi":"10.1017/S0952523824000063","DOIUrl":"10.1017/S0952523824000063","url":null,"abstract":"<p><p>Attention has been shown to modulate the visual evoked potential (VEP) recorded to reversing achromatic patterns. However, the chromatic onset VEP appears to be robust to attentional shifts. Functional magnetic resonance imaging (fMRI) responses to both chromatic and achromatic reversing patterns are also affected by attention. Resolution and comparison of these results is problematic due to differences in presentation mode, stimulus parameters, and the source of the response. Here, we report the results of experiments using comparable perceptual contrasts, pattern reversals, and a co-extensive and highly demanding multiple object tracking (MOT) task while exploring the effects of attentional modulation across both the chromatic (L - M) and (S - (L + M)) and the achromatic visual pathways. Our findings indicate that although achromatic VEPs are modulated by attention, chromatic VEPs are more robust to attentional modulation, even when using comparable stimulus presentation modes and in the presence of a highly demanding distractor task. In addition, we found that the majority of the modulation appears to be from a relative decrease in response due to the distractor task rather than a relative increase in response during heightened attention to the stimulus.</p>","PeriodicalId":23556,"journal":{"name":"Visual Neuroscience","volume":"41 ","pages":"E006"},"PeriodicalIF":1.1,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11731005/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142829514","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The interaction between luminance polarity grouping and symmetry axes on the ERP responses to symmetry.","authors":"Benjamin Dering, Damien Wright, Elena Gheorghiu","doi":"10.1017/S0952523824000075","DOIUrl":"10.1017/S0952523824000075","url":null,"abstract":"<p><p>Symmetry is a salient visual feature in the natural world, yet the perception of symmetry may be influenced by how natural lighting conditions (e.g., shading) fall on the object relative to its symmetry axis. Here, we investigate how symmetry detection may interact with luminance polarity grouping, and whether this modulates neural responses to symmetry, as evidenced by the Sustained Posterior Negativity (SPN) component of Event-Related Potentials (ERPs). Stimuli were dot patterns arranged either symmetrically (reflection, rotation, translation) or quasi-randomly, and by luminance polarity about a grouping axis (i.e., black dots on one side and white dots on the other). We varied the relative angular separation between the symmetry and polarity-grouping axes: 0, 30, 60, 90 deg. Participants performed a two interval-forced-choice (2IFC) task indicating which interval contained the symmetrical pattern. We found that accuracy for the 0 deg polarity-grouped condition was higher compared to the single-polarity condition for rotation and translation (but not reflection symmetry), and higher than all other angular difference (30, 60, 90) conditions for all symmetry types. The SPN was found to be separated topographically into an early and late component, with the early SPN being sensitive to luminance polarity grouping at parietal-occipital electrodes, and the late SPN sensitive to symmetry over central electrodes. The increase in relative angular differences between luminance polarity and symmetry axes highlighted changes between cardinal (0, 90 deg) and other (30, 60 deg) angles. Critically, we found a polarity-grouping effect in the SPN time window for noise only patterns, which was related to symmetry type, suggesting a task/ symmetry pattern influence on SPN processes. We conclude that luminance polarity grouping can facilitate symmetry perception when symmetry is not readily salient, as evidenced by polarity sensitivity of early SPN, yet it can also inhibit neural and behavioral responses when luminance polarity and symmetry axes are not aligned.</p>","PeriodicalId":23556,"journal":{"name":"Visual Neuroscience","volume":"41 ","pages":"E005"},"PeriodicalIF":1.1,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11730996/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142829692","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Electroretinographic responses to periodic stimuli in primates and the relevance for visual perception and for clinical studies.","authors":"Jan Kremers, Cord Huchzermeyer","doi":"10.1017/S0952523824000038","DOIUrl":"10.1017/S0952523824000038","url":null,"abstract":"<p><p>Currently, electroretinograms (ERGs) are mainly recorded while using flashes as stimuli. In this review, we will argue that strong flashes are not ideal for studying visual information processing. ERG responses to periodic stimuli may be more strongly associated with the activity of post-receptoral neurons (belonging to different retino-geniculate pathways) and, therefore, be more relevant for visual perception. We will also argue that the use of periodic stimuli may be an attractive addition to clinically available retinal electrophysiological methods.</p>","PeriodicalId":23556,"journal":{"name":"Visual Neuroscience","volume":"41 ","pages":"E004"},"PeriodicalIF":1.1,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11579838/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142629169","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chris S. Mesnard, Cassandra L. Hays, Lou E. Townsend, Cody L. Barta, Channabasavaiah B. Gurumurthy, Wallace B. Thoreson
{"title":"Synaptotagmin-9 in mouse retina","authors":"Chris S. Mesnard, Cassandra L. Hays, Lou E. Townsend, Cody L. Barta, Channabasavaiah B. Gurumurthy, Wallace B. Thoreson","doi":"10.1017/s0952523824000026","DOIUrl":"https://doi.org/10.1017/s0952523824000026","url":null,"abstract":"Synaptotagmin-9 (Syt9) is a Ca<jats:sup>2+</jats:sup> sensor mediating fast synaptic release expressed in various parts of the brain. The presence and role of Syt9 in retina is unknown. We found evidence for Syt9 expression throughout the retina and created mice to conditionally eliminate Syt9 in a cre-dependent manner. We crossed Syt9<jats:sup>fl/fl</jats:sup> mice with Rho-iCre, HRGP-Cre, and CMV-Cre mice to generate mice in which Syt9 was eliminated from rods (rod<jats:sup>Syt9CKO</jats:sup>), cones (cone<jats:sup>Syt9CKO</jats:sup>), or whole animals (CMV<jats:sup>Syt9</jats:sup>). CMV<jats:sup>Syt9</jats:sup> mice showed an increase in scotopic electroretinogram (ERG) b-waves evoked by bright flashes with no change in a-waves. Cone-driven photopic ERG b-waves were not significantly different in CMV<jats:sup>Syt9</jats:sup> knockout mice and selective elimination of Syt9 from cones had no effect on ERGs. However, selective elimination from rods decreased scotopic and photopic b-waves as well as oscillatory potentials. These changes occurred only with bright flashes where cone responses contribute. Synaptic release was measured in individual rods by recording anion currents activated by glutamate binding to presynaptic glutamate transporters. Loss of Syt9 from rods had no effect on spontaneous or depolarization-evoked release. Our data show that Syt9 acts at multiple sites in the retina and suggest that it may play a role in regulating transmission of cone signals by rods.","PeriodicalId":23556,"journal":{"name":"Visual Neuroscience","volume":"2 1","pages":""},"PeriodicalIF":1.9,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142259182","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hannah M Follett, Emma Warr, Jenna Grieshop, Ching Tzu Yu, Mina Gaffney, Owen R Bowie, Jong Won Lee, Sergey Tarima, Dana K Merriman, Joseph Carroll
{"title":"Chemically induced cone degeneration in the 13-lined ground squirrel.","authors":"Hannah M Follett, Emma Warr, Jenna Grieshop, Ching Tzu Yu, Mina Gaffney, Owen R Bowie, Jong Won Lee, Sergey Tarima, Dana K Merriman, Joseph Carroll","doi":"10.1017/S0952523824000014","DOIUrl":"10.1017/S0952523824000014","url":null,"abstract":"<p><p>Animal models of retinal degeneration are critical for understanding disease and testing potential therapies. Inducing degeneration commonly involves the administration of chemicals that kill photoreceptors by disrupting metabolic pathways, signaling pathways, or protein synthesis. While chemically induced degeneration has been demonstrated in a variety of animals (mice, rats, rabbits, felines, 13-lined ground squirrels (13-LGS), pigs, chicks), few studies have used noninvasive high-resolution retinal imaging to monitor the <i>in vivo</i> cellular effects. Here, we used longitudinal scanning light ophthalmoscopy (SLO), optical coherence tomography, and adaptive optics SLO imaging in the euthermic, cone-dominant 13-LGS (46 animals, 52 eyes) to examine retinal structure following intravitreal injections of chemicals, which were previously shown to induce photoreceptor degeneration, throughout the active season of 2019 and 2020. We found that iodoacetic acid induced severe pan-retinal damage in all but one eye, which received the lowest concentration. While sodium nitroprusside successfully induced degeneration of the outer retinal layers, the results were variable, and damage was also observed in 50% of contralateral control eyes. Adenosine triphosphate and tunicamycin induced outer retinal specific damage with varying results, while eyes injected with thapsigargin did not show signs of degeneration. Given the variability of damage we observed, follow-up studies examining the possible physiological origins of this variability are critical. These additional studies should further advance the utility of chemically induced photoreceptor degeneration models in the cone-dominant 13-LGS.</p>","PeriodicalId":23556,"journal":{"name":"Visual Neuroscience","volume":"41 ","pages":"E002"},"PeriodicalIF":6.5,"publicationDate":"2024-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11106521/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140897332","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}