Vision Research最新文献

{"title":"Intravitreal AAV2 gene delivery to feline retinal ganglion cells","authors":"Kazuya Oikawa ,&nbsp;J.Seth Eaton ,&nbsp;Julie A. Kiland ,&nbsp;Odalys Torné ,&nbsp;Virginia Mathu ,&nbsp;Robert W. Nickells ,&nbsp;Gillian J. McLellan","doi":"10.1016/j.visres.2024.108519","DOIUrl":"10.1016/j.visres.2024.108519","url":null,"abstract":"<div><div>Effective strategies for the neuroprotection and preservation of retinal ganglion cells (RGCs) remain elusive in the management of glaucoma. A spontaneous genetic model of glaucoma has been identified in cats and extensively characterized as a viable translational model, with eye size and anatomy similar to humans. In this study we sought to establish initial proof of concept for gene delivery to feline RGCs via intravitreal injection of AAV2 in normal cats<em>.</em> Pre-retinal, posterior vitreal injection of AAV2/2-CMV-GFP, was performed overlying the area centralis in 5 adult cats. Immunosuppressive oral prednisolone was administered perioperatively and gradually tapered over 6-10wks post-injection. Ophthalmic examination was performed pre- and post-injection. The GFP reporter expression and morphological effects of viral transduction on the retina were monitored <em>in vivo</em> using confocal scanning laser ophthalmoscopy (cSLO) and optical coherence tomography (OCT), respectively (Spectralis OCT-HRA, Heidelberg), at 1-2wk intervals over 6-10wks. Full-field electroretinograms (ERG) and visual evoked potentials (VEP) were recorded at baseline and post-injection. Retinas were examined by histology and immunolabeling for the RGC marker RBPMS and Müller cell and astrocyte marker SOX9, and GFP expression was examined in the retina, optic nerve (ON), optic tract and lateral geniculate nucleus (LGN). GFP⁺ retinal cells and RGC axons were visualized by cSLO at 1–2 weeks post-injection. No retinal morphological changes were observed by OCT <em>in vivo</em> but 3/5 eyes exhibited mild retinal inflammation on histology. Retinal and ON function were preserved in injected eyes compared to baseline and untreated eyes. GFP expression was predominantly identified in RBPMS⁺ RGC cells as well as SOX9⁺ Müller cells. GFP fluorescence was observed throughout RGC nerve fiber tract in the central visual pathway. Peak transduction in RGCs (up to ∼ 20 %) was observed in the regions with high GFP expression, but &lt; 1 % of RGCs expressed GFP across the whole retina. Our data provide proof of concept that pre-retinal injection of AAV2/2 may represent a feasible platform for gene delivery to feline RGCs <em>in vivo</em> but highlight a need for further refinement to improve RGC transduction efficiency and control low-grade retinal inflammation.</div></div>","PeriodicalId":23670,"journal":{"name":"Vision Research","volume":"226 ","pages":"Article 108519"},"PeriodicalIF":1.5,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142645033","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exfoliation syndrome genetics in the era of post-GWAS","authors":"Ola A. Elsayed ,&nbsp;Jingwen Cai ,&nbsp;Yutao Liu","doi":"10.1016/j.visres.2024.108518","DOIUrl":"10.1016/j.visres.2024.108518","url":null,"abstract":"<div><div>Exfoliation syndrome (XFS), or pseudoexfoliation syndrome, is considered a systemic disorder that leads to glaucoma with progressive visual field loss. A better insight into the underlying pathogenic mechanism will help diagnose the disease and prevent and slow progression. Here, we provide an overview of disease pathogenesis in the light of GWAS and multi-omics research. We discuss possible environmental interactions related to XFS. We investigate the potential interactions in differentially expressed genes from RNA-Seq by using Ingenuity Pathway Analysis. MAPK pathway was identified as the top network of these genes. Further investigation is needed to verify our results in vivo. It is necessary to establish an animal model mimicking exfoliation syndrome phenotypes.</div></div>","PeriodicalId":23670,"journal":{"name":"Vision Research","volume":"226 ","pages":"Article 108518"},"PeriodicalIF":1.5,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142645032","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lack of retinal degeneration in a Dram2 knockout mouse model","authors":"Kuanxiang Sun ,&nbsp;Junyao Chen ,&nbsp;Yudi Fan ,&nbsp;Jinrui Cai ,&nbsp;Xiaoyan Jiang ,&nbsp;Wenjing Liu ,&nbsp;Xianjun Zhu","doi":"10.1016/j.visres.2024.108509","DOIUrl":"10.1016/j.visres.2024.108509","url":null,"abstract":"<div><div>Damage-regulated autophagy modulator 2 (DRAM2) is a homologue of the DRAM family protein, which can induce autophagy process. In the retina, DRAM2 is located to the inner segment of photoreceptors, the apical surface of retinal pigment epithelial (RPE) cells, and the lysosome. Pathogenic variants of <em>DRAM2</em> lead to autosomal recessive Cone-rod dystrophy 21 (CORD21). Cone-rod dystrophy is characterised by primary cone involvement, or sometimes simultaneous cone and rod loss, thus leading to decreased visual acuity, colour vision deficits, photophobia, and decreased sensitivity of the central visual field. However, the mechanisms underlying <em>DRAM2</em> related retinal diseases remained unclear. To further explore the role of <em>Dram2</em> in the retina, we generated <em>Dram2</em> knockout mice (KO) by CRISPR/Cas-9 technology and demonstrated that expression of DRAM2 was abolished in KO retinas. <em>Dram2</em> ablation failed to manifest any retinal degenerative phenotypes. <em>Dram2</em> KO did not exhibit visible defect in photo response and the overt structure of the retinas. Immunostaing analysis using antibodies against cone opsins revealed no detectable loss of cone cells. Moreover, no visible change was observed in the expression and localisation of rhodopsin and other membrane disc proteins in <em>Dram2</em> KO retinas and no gliosis and apoptosis were detected in KO mice. In summary, these data revealed lack of overt retinal degeneration in <em>Dram2</em> KO model and emphasized the importance of further investigation of the mechanisms underlying Cone-rod dystrophy 21.</div></div>","PeriodicalId":23670,"journal":{"name":"Vision Research","volume":"226 ","pages":"Article 108509"},"PeriodicalIF":1.5,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142628648","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Structural framework to address variant-gene relationship in primary open-angle glaucoma","authors":"Nivedita Singh ,&nbsp;Krishnakumar Kizhatil ,&nbsp;Durairaj Duraikannu ,&nbsp;Hélène Choquet ,&nbsp;K. Saidas Nair","doi":"10.1016/j.visres.2024.108505","DOIUrl":"10.1016/j.visres.2024.108505","url":null,"abstract":"<div><div>Primary open-angle glaucoma (POAG) is a complex, multifactorial disease leading to progressive optic neuropathy and irreversible vision loss. Genome-Wide Association Studies (GWAS) have significantly advanced our understanding of the genetic loci associated with POAG. Expanding on these findings, Exome-Wide Association Studies (ExWAS) refine the genetic landscape by identifying rare coding variants with potential functional relevance. Post-GWAS <em>in silico</em> analyses, including fine-mapping, gene-based association testing, and pathway analysis, offer insights into target genes and biological mechanisms underlying POAG. This review aims to provide a comprehensive roadmap for the post-GWAS characterization of POAG genes. We integrate current knowledge from GWAS, ExWAS, and post-GWAS analyses, highlighting key genetic variants and pathways implicated in POAG. Recent advancements in genomics, such as ATAC-seq, CUT&amp;RUN, and Hi-C, are crucial for identifying disease-relevant gene regulatory elements by profiling chromatin accessibility, histone modifications, and three-dimensional chromatin architecture. These approaches help pinpoint regulatory elements that influence gene expression in POAG. Expression Quantitative Trait Loci (eQTL) analysis and Transcriptome-Wide Association Studies (TWAS) elucidate the impact of these elements on gene expression and disease risk, while functional validations like enhancer reporter assays confirm their relevance. The integration of high-resolution genomics with functional assays and the characterization of genes <em>in vivo</em> using animal models provides a robust framework for unraveling the complex genetic architecture of POAG. This roadmap is essential for advancing our understanding and identification of genes and regulatory networks involved in POAG pathogenesis.</div></div>","PeriodicalId":23670,"journal":{"name":"Vision Research","volume":"226 ","pages":"Article 108505"},"PeriodicalIF":1.5,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142628803","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Towards a principled and efficacious approach to the treatment of amblyopia. A review","authors":"Robert F. Hess","doi":"10.1016/j.visres.2024.108503","DOIUrl":"10.1016/j.visres.2024.108503","url":null,"abstract":"<div><div>There is currently a diverse array of treatment for amblyopia. In addition to the traditional penalization therapy, which has been used for over 200 years, there are not only more active treatments to recover the monocular visual loss of the amblyopic eye involving both behavioral (visual training) as well as non-invasive brain stimulation but also a variety of methods designed specifically to restore binocular function. Our understanding of visual function in general and of the etiology of the amblyopic loss in particular has progressed a great deal over the last 50 years and it is now time to take a more principled approach to how we treat, when we treat and why we treat.</div></div>","PeriodicalId":23670,"journal":{"name":"Vision Research","volume":"226 ","pages":"Article 108503"},"PeriodicalIF":1.5,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142605212","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Depth constancy and the absolute vergence anomaly","authors":"Rebecca E. Ranson ,&nbsp;Peter Scarfe ,&nbsp;Loes C.J. van Dam ,&nbsp;Paul B. Hibbard","doi":"10.1016/j.visres.2024.108501","DOIUrl":"10.1016/j.visres.2024.108501","url":null,"abstract":"<div><div>Binocular disparity provides information about the depth structure of objects and surfaces in our environment. Since disparity depends on the distance to objects as well as the depth separation of points, information about distance is required to estimate depth from disparity. Our perception of size and shape is biased, such that far objects appear too small and flattened in depth, and near objects too big and stretched in depth. The current study assessed the extent to which the failure of depth constancy can be accounted for by the uncertainty of distance information provided by vergence. We measured individual differences in vergence noise using a nonius line task, and the degree of depth constancy using a task in which observers judged the magnitude of a depth interval relative to the vertical distance between two targets in the image plane. We found no correlation between the two measures, and show that depth constancy was much poorer than would be expected from vergence noise measured in this way. This limited ability to take account of vergence in the perception of depth is, however, consistent with our poor sensitivity to absolute disparity differences. This absolute disparity anomaly thus also applies to our poor ability to make use of vergence information for absolute distance judgements.</div></div>","PeriodicalId":23670,"journal":{"name":"Vision Research","volume":"226 ","pages":"Article 108501"},"PeriodicalIF":1.5,"publicationDate":"2024-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142569739","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ATXN2 loss of function results in glaucoma-related features supporting a role for Ataxin-2 in primary open-angle glaucoma (POAG) pathogenesis","authors":"Shi Song Rong,&nbsp;Anna Larson,&nbsp;Janey L. Wiggs,&nbsp;NEIGHBORHOOD consortium","doi":"10.1016/j.visres.2024.108508","DOIUrl":"10.1016/j.visres.2024.108508","url":null,"abstract":"<div><div>Glaucoma is a leading cause of irreversible blindness worldwide. The most common form, primary open-angle glaucoma (POAG), is a genetically complex trait with high heritability. Genome-wide association studies have identified significant POAG and IOP association of a genomic region on chromosome 12 that includes <em>ATXN2</em> as well as 7 other genes. Association of protein disrupting <em>ATXN2</em> variants in the NEIGHBORHOOD case-control cohort and the UK Biobank suggests that <em>ATXN2</em> is a key gene in this locus. To investigate functional effects, we utilized a zebrafish (Danio rerio) CRISPR/Cas9 edited <em>atxn2</em>-knockdown line to show that loss of <em>atxn2</em> results in reduced eye size, diminished retinal ganglion cells (RGC), increased intraocular pressure (IOP), and impaired visual function in zebrafish. Complementation assays supported functional effects for 14 POAG-associated human <em>ATXN2</em> missense variants. These results suggest a loss-of-function mechanism underlying a potential role for <em>ATXN2</em> in POAG pathogenesis.</div></div>","PeriodicalId":23670,"journal":{"name":"Vision Research","volume":"226 ","pages":"Article 108508"},"PeriodicalIF":1.5,"publicationDate":"2024-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142569737","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Accentuation, Boolean maps and perception of (dis)similarity in a neural model of visual segmentation","authors":"Dražen Domijan,&nbsp;Ivana Ivančić","doi":"10.1016/j.visres.2024.108506","DOIUrl":"10.1016/j.visres.2024.108506","url":null,"abstract":"<div><div>We developed an interactive cortical circuit for visual segmentation that integrates bottom-up and top-down processing to segregate or group visual elements. A bottom-up pathway incorporates stimulus-driven saliency computation, top-down feature-based weighting by relevance and winner-take-all selection. A top-down pathway encompasses multiscale feedback projections, an object-based attention network and a visual segmentation network. Computer simulations have shown that a salient element in the stimulus guides spatial attention and further influences the decomposition of the nearby object into its parts, as postulated by the principle of accentuation. By contrast, when no single salient element is present, top-down feature-based attention highlights all locations occupied by the attended feature and the model forms a Boolean map, i.e., a spatial representation that makes the feature-based grouping explicit. The same distinction between bottom-up and top-down influences in perceptual organization can also be applied to texture perception. The model suggests that the principle of accentuation and feature-based similarity grouping are two manifestations of the same cortical circuit designed to detect similarities and dissimilarities of visual elements in a stimulus.</div></div>","PeriodicalId":23670,"journal":{"name":"Vision Research","volume":"225 ","pages":"Article 108506"},"PeriodicalIF":1.5,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142560784","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ovariectomy drives increase of an ECM transcription signature in the posterior eye and retina","authors":"Cydney A. Wong ,&nbsp;Gabriela Sanchez-Rodriguez ,&nbsp;C. Ross Ethier ,&nbsp;Levi B. Wood ,&nbsp;Andrew J. Feola","doi":"10.1016/j.visres.2024.108507","DOIUrl":"10.1016/j.visres.2024.108507","url":null,"abstract":"<div><div>Increased risk of developing glaucoma has recently been associated with early age of menopause. Here, we examined how age and surgically-induced menopause via ovariectomy (OVX) impacted gene expression in gene pathways previously linked to glaucoma, such as extracellular matrix (ECM) remodeling and TGF-β signaling. Using bulk RNA sequencing, we analyzed changes in young (3–4 months) and middle-aged (9–10 months) Long-Evans rats. We focused on posterior pole tissues (sclera and optic nerve head) but also examined the retina to compare observed changes across different tissue regions. Our results demonstrated that aging and OVX significantly alter gene expression in the sclera and optic nerve head. Generally, OVX triggered the enrichment of immune-related processes. However, OVX in young rats also led to significant enrichment of ECM and TGF-β gene sets. At the same time, these effects were diminished in middle-aged rats, indicating an age dependency of the effects of OVX on matrix-related pathways. Notably, the transcriptional factor <em>Fos</em> was downregulated in the posterior eye and retina in aged and OVX animals. <em>Fos</em> is a major regulator of cell proliferation and survival, and its dysregulation may play an important role in aging and menopause for women. These findings underscore the important role of menopause timing in modulating molecular pathways associated with glaucoma, which is consistent with clinical studies showing that early menopause may heighten the risk of developing this condition. This study also highlights the importance of considering women’s health factors, such as menopause, in understanding and managing glaucoma risk.</div></div>","PeriodicalId":23670,"journal":{"name":"Vision Research","volume":"225 ","pages":"Article 108507"},"PeriodicalIF":1.5,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142547831","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The concept of group and the theory of perception","authors":"Gerald Westheimer","doi":"10.1016/j.visres.2024.108504","DOIUrl":"10.1016/j.visres.2024.108504","url":null,"abstract":"<div><div>Prompted by the title of Ernst <span><span>Cassirer’s 1944</span></span> essay, the origin of the idea of a Group theoretical approach, in the mathematical sense, in vision science is here explored, as well as the several ways in which its implementation had been attempted. That object recognition might proceed by a more generative approach rather than by separate individual cataloging had already been argued by Kant, and Cassirer examined how mathematical group theory might be called on for this purpose, in view of the success of its use in geometry and in the physical sciences. However, such a promise appears unlikely in view of the categorical differences between analysis of mental phenomena and of the physical world.</div></div>","PeriodicalId":23670,"journal":{"name":"Vision Research","volume":"225 ","pages":"Article 108504"},"PeriodicalIF":1.5,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142531821","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}