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Effects of cue location and object orientation on object-based attention. 线索位置和物体方位对基于物体的注意力的影响
IF 1.5 4区 心理学 Q4 NEUROSCIENCES Pub Date : 2024-11-19 DOI: 10.1016/j.visres.2024.108521
Hao Lou, Karin S Pilz, Monicque M Lorist

Spatial cues have previously been found to facilitate information processing not only at cued locations but also within cued objects, so-called object-based attention. We used different variants of the classic two-rectangle paradigm to investigate the interaction of cue location and object orientation on object-based attentional effects. First, we re-analyzed data from a prior study using the classical two-rectangle paradigm. We expected faster attentional shifts along the horizontal compared to the vertical meridian. Results confirmed that cue location and rectangle orientation interactively influence object-based attention, with horizontal objects combined with upper left visual field cues eliciting faster responses than other conditions. In Experiment 2, we removed object contours to examine the benefits of shifting attention based purely on cue location. The results showed that these differences remained, indicating that attentional shifts are not solely guided by object contours. In Experiment 3, we added a third possible target location to the original two-rectangle experiment to examine whether attentional shifts followed a predictable pattern across the stimulus display. Despite faster responses to cued targets, no consistent and organized visual search pattern was observed when participants searched for targets at invalidly cued locations. Our findings suggest that object-based effects are influenced by both cue location and the orientation of attentional shifts. Shifts from left to right in the upper visual field consistently demonstrated significant benefits, whereas the benefits of vertical shifts were less consistent across experiments.

以前曾有研究发现,空间线索不仅能促进提示位置的信息处理,还能促进提示对象内部的信息处理,即所谓的基于对象的注意。我们使用了经典双角范式的不同变体来研究线索位置和对象方位对基于对象的注意效应的交互作用。首先,我们重新分析了之前使用经典双矩形范式研究的数据。我们预计,与垂直经线相比,沿水平经线的注意力转移速度更快。结果证实,提示位置和矩形方向会交互影响基于物体的注意力,与其他条件相比,水平物体与左上方视野提示相结合会引起更快的反应。在实验 2 中,我们去掉了物体轮廓,以研究纯粹根据提示位置转移注意力的益处。结果显示,这些差异依然存在,表明注意力的转移并不完全受物体轮廓线的引导。在实验 3 中,我们在原来的双矩形实验中增加了第三个可能的目标位置,以考察注意力转移是否遵循整个刺激显示的可预测模式。尽管被试对提示目标的反应更快,但当被试在无效提示位置搜索目标时,并没有观察到一致且有组织的视觉搜索模式。我们的研究结果表明,基于目标的效应同时受到提示位置和注意力转移方向的影响。在上视野中从左到右的转移始终表现出显著的益处,而垂直转移的益处在不同实验中的表现则不太一致。
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引用次数: 0
Intravitreal AAV2 gene delivery to feline retinal ganglion cells 将 AAV2 基因植入猫视网膜神经节细胞。
IF 1.5 4区 心理学 Q4 NEUROSCIENCES Pub Date : 2024-11-16 DOI: 10.1016/j.visres.2024.108519
Kazuya Oikawa , J.Seth Eaton , Julie A. Kiland , Odalys Torné , Virginia Mathu , Robert W. Nickells , Gillian J. McLellan
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. 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 in vivo 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 in vivo 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 < 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 in vivo but highlight a need for further refinement to improve RGC transduction efficiency and control low-grade retinal inflammation.
在治疗青光眼的过程中,神经保护和保留视网膜神经节细胞(RGC)的有效策略仍然难以捉摸。在猫身上发现了一种自发的青光眼遗传模型,并将其广泛表征为一种可行的转化模型,其眼睛大小和解剖结构与人类相似。在这项研究中,我们试图在正常猫体内通过玻璃体内注射 AAV2 将基因传递到猫的 RGCs,并对这一概念进行初步验证。我们在 5 只成年猫的中央区上方进行了 AAV2/2-CMV-GFP 视网膜前、后玻璃体内注射。围手术期口服泼尼松龙进行免疫抑制,并在注射后 6-10 周内逐渐减量。注射前后均进行了眼科检查。在6-10周内,每隔1-2周分别使用共焦扫描激光眼底镜(cSLO)和光学相干断层扫描(OCT)(Spectralis OCT-HRA,海德堡)监测GFP报告表达和病毒转导对视网膜的形态学影响。在基线和注射后记录全场视网膜电图(ERG)和视觉诱发电位(VEP)。通过组织学和免疫标记RGC标记物RBPMS及Müller细胞和星形胶质细胞标记物SOX9检查视网膜,并检查视网膜、视神经(ON)、视束和外侧膝状核(LGN)中的GFP表达。注射后1-2周,通过cSLO观察GFP+视网膜细胞和RGC轴突。活体 OCT 未观察到视网膜形态学变化,但有 3/5 的眼睛在组织学上表现出轻微的视网膜炎症。与基线和未处理的眼睛相比,注射眼的视网膜和视网膜功能都得到了保留。GFP 主要在 RBPMS+ RGC 细胞和 SOX9+ Müller 细胞中表达。在中央视觉通路的整个 RGC 神经纤维束中都能观察到 GFP 荧光。在 GFP 高表达区域观察到 RGC 的峰值转导(高达 ∼ 20 %),但在 GFP 低表达区域观察到 RGC 的峰值转导(高达 ∼ 20 %)。
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引用次数: 0
Exfoliation syndrome genetics in the era of post-GWAS 后 GWAS 时代的剥脱综合征遗传学。
IF 1.5 4区 心理学 Q4 NEUROSCIENCES Pub Date : 2024-11-16 DOI: 10.1016/j.visres.2024.108518
Ola A. Elsayed , Jingwen Cai , Yutao Liu
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.
剥脱综合征(XFS)或假性剥脱综合征被认为是一种导致青光眼并伴有进行性视野缺损的全身性疾病。更好地了解其潜在的致病机制将有助于诊断该疾病并预防和延缓其发展。在此,我们根据全球基因组分析和多组学研究概述了该疾病的发病机制。我们讨论了与 XFS 相关的可能的环境相互作用。我们利用 Ingenuity Pathway Analysis 对 RNA-Seq 差异表达基因中的潜在相互作用进行了研究。MAPK通路被确定为这些基因的顶级网络。要在体内验证我们的结果,还需要进一步的研究。有必要建立一个模仿剥脱综合征表型的动物模型。
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引用次数: 0
Lack of retinal degeneration in a Dram2 knockout mouse model Dram2 基因敲除小鼠模型缺乏视网膜变性。
IF 1.5 4区 心理学 Q4 NEUROSCIENCES Pub Date : 2024-11-08 DOI: 10.1016/j.visres.2024.108509
Kuanxiang Sun , Junyao Chen , Yudi Fan , Jinrui Cai , Xiaoyan Jiang , Wenjing Liu , Xianjun Zhu
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 DRAM2 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 DRAM2 related retinal diseases remained unclear. To further explore the role of Dram2 in the retina, we generated Dram2 knockout mice (KO) by CRISPR/Cas-9 technology and demonstrated that expression of DRAM2 was abolished in KO retinas. Dram2 ablation failed to manifest any retinal degenerative phenotypes. Dram2 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 Dram2 KO retinas and no gliosis and apoptosis were detected in KO mice. In summary, these data revealed lack of overt retinal degeneration in Dram2 KO model and emphasized the importance of further investigation of the mechanisms underlying Cone-rod dystrophy 21.
损伤调控自噬调节因子2(DRAM2)是DRAM家族蛋白的同源物,可诱导自噬过程。在视网膜中,DRAM2 位于感光器内节、视网膜色素上皮细胞(RPE)顶端表面和溶酶体。DRAM2 的致病变体会导致常染色体隐性遗传的圆锥杆状营养不良症 21(CORD21)。锥状杆营养不良症的特点是原发性锥状体受累,有时锥状体和杆状体同时丧失,从而导致视力下降、色觉障碍、畏光和中央视野敏感度降低。然而,DRAM2 相关视网膜疾病的发病机制仍不清楚。为了进一步探索Dram2在视网膜中的作用,我们通过CRISPR/Cas-9技术产生了Dram2基因敲除小鼠(KO),并证明DRAM2在KO视网膜中的表达被取消。Dram2 消减未能表现出任何视网膜变性表型。Dram2 KO没有表现出明显的光反应缺陷和视网膜的明显结构缺陷。使用针对视锥蛋白的抗体进行的免疫测定分析表明,没有发现视锥细胞的损失。此外,Dram2 KO 小鼠视网膜中的视紫红质和其他膜盘蛋白的表达和定位没有发生明显变化,也没有检测到神经胶质增生和细胞凋亡。总之,这些数据揭示了 Dram2 KO 模型缺乏明显的视网膜变性,并强调了进一步研究 21 型锥体-杆状营养不良症的机制的重要性。
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引用次数: 0
Structural framework to address variant-gene relationship in primary open-angle glaucoma 解决原发性开角型青光眼变异基因关系的结构框架。
IF 1.5 4区 心理学 Q4 NEUROSCIENCES Pub Date : 2024-11-08 DOI: 10.1016/j.visres.2024.108505
Nivedita Singh , Krishnakumar Kizhatil , Durairaj Duraikannu , Hélène Choquet , K. Saidas Nair
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 in silico 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&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 in vivo 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.
原发性开角型青光眼(POAG)是一种复杂的多因素疾病,会导致进行性视神经病变和不可逆的视力丧失。全基因组关联研究(GWAS)极大地促进了我们对 POAG 相关基因位点的了解。在这些研究结果的基础上,全基因组关联研究(ExWAS)通过鉴定具有潜在功能相关性的罕见编码变异,完善了遗传图谱。全基因组关联研究后的硅学分析,包括精细图谱绘制、基于基因的关联测试和通路分析,可帮助人们深入了解 POAG 的靶基因和生物学机制。本综述旨在提供一个全面的 POAG 基因 GWAS 后特征描述路线图。我们整合了 GWAS、ExWAS 和后 GWAS 分析的现有知识,重点介绍了与 POAG 相关的关键基因变异和通路。基因组学的最新进展,如 ATAC-seq、CUT&RUN 和 Hi-C,对于通过分析染色质可及性、组蛋白修饰和三维染色质结构来确定与疾病相关的基因调控元件至关重要。这些方法有助于确定影响 POAG 基因表达的调控元件。表达定量性状位点(eQTL)分析和全转录组关联研究(TWAS)阐明了这些元件对基因表达和疾病风险的影响,而增强子报告实验等功能验证则证实了它们的相关性。高分辨率基因组学与功能检测的整合,以及利用动物模型对体内基因进行表征,为揭示 POAG 复杂的遗传结构提供了一个强有力的框架。这一路线图对于加深我们对参与 POAG 发病机制的基因和调控网络的理解和鉴定至关重要。
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引用次数: 0
Towards a principled and efficacious approach to the treatment of amblyopia. A review 为治疗弱视制定原则性的有效方法。综述。
IF 1.5 4区 心理学 Q4 NEUROSCIENCES Pub Date : 2024-11-07 DOI: 10.1016/j.visres.2024.108503
Robert F. Hess
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.
目前,治疗弱视的方法多种多样。除了已经使用了 200 多年的传统惩罚疗法外,还有更积极的疗法来恢复弱视眼的单眼视力损失,包括行为疗法(视觉训练)和非侵入性脑部刺激疗法,以及各种专门用于恢复双眼功能的方法。在过去的 50 年中,我们对视觉功能,特别是弱视病因的认识有了长足的进步,现在是时候对如何治疗、何时治疗以及为何治疗采取更有原则性的方法了。
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引用次数: 0
Depth constancy and the absolute vergence anomaly 深度恒定和绝对辐辏异常。
IF 1.5 4区 心理学 Q4 NEUROSCIENCES Pub Date : 2024-11-02 DOI: 10.1016/j.visres.2024.108501
Rebecca E. Ranson , Peter Scarfe , Loes C.J. van Dam , Paul B. Hibbard
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.
双眼视差提供了我们所处环境中物体和表面的深度结构信息。由于视差取决于与物体的距离以及点与点之间的深度分隔,因此需要有关距离的信息才能通过视差估计深度。我们对物体大小和形状的感知是有偏差的,因此远处的物体看起来太小,深度扁平,而近处的物体则太大,深度拉伸。本研究评估了深度恒定性失效在多大程度上可以通过辐辏提供的距离信息的不确定性来解释。我们使用非半径线任务测量了辐辏噪声的个体差异,并使用一项任务测量了深度恒定性的程度,在这项任务中,观察者根据图像平面上两个目标之间的垂直距离来判断深度间隔的大小。我们发现这两种测量方法之间没有相关性,并表明深度恒定性比通过这种方法测量的辐辏噪声所预期的要差得多。然而,这种在深度知觉中考虑辐辏的有限能力与我们对绝对差距差异的低敏感度是一致的。因此,这种绝对差距异常也适用于我们利用辐辏信息进行绝对距离判断的能力差。
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引用次数: 0
ATXN2 loss of function results in glaucoma-related features supporting a role for Ataxin-2 in primary open-angle glaucoma (POAG) pathogenesis ATXN2 功能缺失会导致青光眼相关特征,支持 Ataxin-2 在原发性开角型青光眼(POAG)发病机制中的作用。
IF 1.5 4区 心理学 Q4 NEUROSCIENCES Pub Date : 2024-11-02 DOI: 10.1016/j.visres.2024.108508
Shi Song Rong, Anna Larson, Janey L. Wiggs, NEIGHBORHOOD consortium
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 ATXN2 as well as 7 other genes. Association of protein disrupting ATXN2 variants in the NEIGHBORHOOD case-control cohort and the UK Biobank suggests that ATXN2 is a key gene in this locus. To investigate functional effects, we utilized a zebrafish (Danio rerio) CRISPR/Cas9 edited atxn2-knockdown line to show that loss of atxn2 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 ATXN2 missense variants. These results suggest a loss-of-function mechanism underlying a potential role for ATXN2 in POAG pathogenesis.
青光眼是导致全球不可逆失明的主要原因。最常见的原发性开角型青光眼(POAG)是一种遗传性状复杂的疾病,遗传率很高。全基因组关联研究发现,POAG 和眼压与 12 号染色体上的一个基因组区域有显著关联,该区域包括 ATXN2 和其他 7 个基因。在 NEIGHBORHOOD 病例对照队列和英国生物库(UK Biobank)中,蛋白质干扰 ATXN2 变体的关联表明,ATXN2 是该基因座中的一个关键基因。为了研究其功能效应,我们利用斑马鱼(Danio rerio)CRISPR/Cas9编辑的atxn2-knockdown品系表明,atxn2缺失会导致斑马鱼眼球缩小、视网膜神经节细胞(RGC)减少、眼压(IOP)升高和视觉功能受损。补体测定证实了 14 个与 POAG 相关的人类 ATXN2 错义变体的功能效应。这些结果表明 ATXN2 在 POAG 发病机制中的潜在作用是一种功能缺失机制。
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引用次数: 0
Accentuation, Boolean maps and perception of (dis)similarity in a neural model of visual segmentation 视觉分割神经模型中的重读、布尔图和(不)相似性感知
IF 1.5 4区 心理学 Q4 NEUROSCIENCES Pub Date : 2024-10-31 DOI: 10.1016/j.visres.2024.108506
Dražen Domijan, Ivana Ivančić
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.
我们开发了一种用于视觉分割的交互式皮层电路,它整合了自下而上和自上而下的处理过程,以分离或分组视觉元素。自下而上的通路包括刺激驱动的显著性计算、自上而下的基于特征的相关性加权和赢家通吃选择。自上而下的途径包括多尺度反馈投射、基于对象的注意力网络和视觉分割网络。计算机模拟显示,刺激物中的突出元素会引导空间注意力,并进一步影响将附近物体分解成不同部分的过程,这也是突出原理所假定的。与此相反,当没有单一的突出元素时,自上而下的基于特征的注意会突出被注意特征所占据的所有位置,模型会形成布尔图,即一种空间表征,明确显示基于特征的分组。自下而上和自上而下对知觉组织的影响之间的区别同样适用于纹理知觉。该模型表明,突出原理和基于特征的相似性分组是同一皮层电路的两种表现形式,旨在检测刺激物中视觉元素的相似性和不相似性。
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引用次数: 0
Ovariectomy drives increase of an ECM transcription signature in the posterior eye and retina 卵巢切除术促使后眼和视网膜中的 ECM 转录特征增加。
IF 1.5 4区 心理学 Q4 NEUROSCIENCES Pub Date : 2024-10-30 DOI: 10.1016/j.visres.2024.108507
Cydney A. Wong , Gabriela Sanchez-Rodriguez , C. Ross Ethier , Levi B. Wood , Andrew J. Feola
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 Fos was downregulated in the posterior eye and retina in aged and OVX animals. Fos 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.
最近,青光眼发病风险的增加与绝经年龄过早有关。在这里,我们研究了年龄和通过卵巢切除术(OVX)手术诱导的绝经如何影响先前与青光眼相关的基因通路的基因表达,如细胞外基质(ECM)重塑和 TGF-β 信号转导。我们利用大量 RNA 测序分析了幼年(3-4 个月)和中年(9-10 个月)长伊万斯大鼠的变化。我们重点研究了后极组织(巩膜和视神经头),但也检查了视网膜,以比较不同组织区域观察到的变化。我们的研究结果表明,衰老和 OVX 显著改变了巩膜和视神经头的基因表达。一般来说,OVX 会引发免疫相关过程的丰富化。然而,年轻大鼠的 OVX 也会导致 ECM 和 TGF-β 基因组的显著丰富。与此同时,这些影响在中年大鼠中减弱,这表明 OVX 对基质相关途径的影响与年龄有关。值得注意的是,转录因子 Fos 在老年和 OVX 动物的后眼和视网膜中下调。Fos 是细胞增殖和存活的主要调节因子,它的失调可能在女性衰老和更年期中扮演重要角色。这些发现强调了绝经时间在调节与青光眼相关的分子通路中的重要作用,这与临床研究显示绝经过早可能会增加患青光眼的风险是一致的。这项研究还强调了在了解和管理青光眼风险时考虑更年期等女性健康因素的重要性。
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