Experimental eye research最新文献

{"title":"Plasma N-glycan signature as biomarker for primary open angle glaucoma","authors":"Tsz Kin Ng ,&nbsp;Chunxian Zhang ,&nbsp;Qingping Liu ,&nbsp;Shao-Lang Chen ,&nbsp;Chukai Huang ,&nbsp;Wanli Song ,&nbsp;Chong-Bo Chen ,&nbsp;Yingjie Cao ,&nbsp;Kunliang Qiu ,&nbsp;Li Jia Chen ,&nbsp;Wenzhe Li ,&nbsp;Chi Pui Pang ,&nbsp;Wei Wang ,&nbsp;Mingzhi Zhang","doi":"10.1016/j.exer.2025.110676","DOIUrl":"10.1016/j.exer.2025.110676","url":null,"abstract":"<div><div>Primary open angle glaucoma (POAG) is a major subtype of glaucoma and a leading cause of irreversible visual impairment and blindness worldwide, but with elusive pathogenesis. Here we aimed to delineate the N-glycan profile in the plasma samples of POAG patients and compare to that of the mild senile cataract subjects. Fasting peripheral whole blood was collected from 44 unrelated Han Chinese POAG patients and 39 mild senile cataract subjects. The plasma samples were isolated and subjected to the N-glycan profiling analysis by high throughput fluorophore-assisted capillary gel electrophoreses in an DNA sequencer. In total, 21 major asialo N-glycan peaks were observed in the plasma samples of the POAG patients and cataract subjects through the capillary gel electrophoresis analysis. Relative peak height proportions of Peak III, VIII, and X showed significant differences in the POAG patients as compared to the cataract subjects, and combined Peak III, VIII, and X achieved an AUC of 0.792. Linear correlation analysis revealed a negative correlation of Peak X with mean deviation of visual field in the POAG patients. Notably, sex-specific N-glycan differences were observed. Lectin blotting demonstrated higher level of core fucosylation on the plasma immunoglobulin G of the POAG patients. In summary, this study revealed the N-glycan profiles in the plasma samples of POAG patients. The plasma N-glycan signature can be a potential novel biomarker for POAG.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"261 ","pages":"Article 110676"},"PeriodicalIF":2.7,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145212012","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ABCA4-Mutant Human Retinal Organoids Sequencing Reveals Organoids Application in Inherited Retinal Diseases.","authors":"Yourong Bao, Sujung Soh, Jean Li, Zhen Zuo, Salma Ferdous, Xinye Qian, Jin Li, Jiaxiong Lu, Xuesen Cheng, Anna Matynia, Yumei Li, Rui Chen","doi":"10.1016/j.exer.2025.110677","DOIUrl":"https://doi.org/10.1016/j.exer.2025.110677","url":null,"abstract":"<p><p>In the studies of Inherited Retinal Diseases (IRDs), the knockout of traditional animal models like mice often fails to accurately replicate human phenotypes due to genetic and anatomical differences. Human retinal organoids (ROs) derived from stem cells have emerged as promising developmental models in retinal studies to delineate cell growth, but their ability to represent the characteristics of late-onset IRDs remains unclear. This study aims to validate ROs as a disease model for Stargardt's Disease (STGD) caused by ABCA4 mutations. Using single-cell RNA sequencing, ROs from 2 STGD patients were compared with healthy control-derived ROs at two developmental stages on both the cellular and transcriptomic levels. The results from gene-level comparisons show promising evidence that ROs successfully capture the underlying molecular variations between patient and control samples even at the early developmental stage, providing the potential of applying ROs to facilitate the study of IRDs and late-onset neurodegenerative diseases.</p>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":" ","pages":"110677"},"PeriodicalIF":2.7,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145212019","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lactate metabolism and lactylation in ocular diseases","authors":"Yue Zhou ,&nbsp;Wengen Zhu ,&nbsp;Xi Yin ,&nbsp;Minzhi Zeng ,&nbsp;Junming Wang","doi":"10.1016/j.exer.2025.110674","DOIUrl":"10.1016/j.exer.2025.110674","url":null,"abstract":"<div><div>Lactate, once considered a mere metabolic byproduct of anaerobic glycolysis, has undergone a paradigm shift in its biological significance. Emerging evidence now positions it as a central regulator of cellular metabolism, signaling, and disease pathophysiology across diverse tissues, including the retina and other ocular structures. The retina, as a highly metabolically active and oxygen-demanding tissue, presents a unique landscape for lactate dynamics. Its reliance on aerobic glycolysis leads to substantial lactate production even under normoxic conditions. This metabolic strategy, while ensuring rapid adenosine triphosphate generation, also positions lactate as both an energy currency and a signaling molecule, with significant implications for retinal homeostasis and diseases. This review summarizes current advances in understanding lactate metabolism and its newly discovered post-translational modification, lactylation, in the context of major ocular pathologies, including myopia, ocular melanoma, autoimmune uveitis, and retinal neovascularization. By bridging molecular mechanisms with clinical implications, we aim to illuminate lactate's dual roles as a metabolic substrate and an epigenetic modulator in ocular health and diseases.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"261 ","pages":"Article 110674"},"PeriodicalIF":2.7,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145206108","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chondroitin sulfate and hyaluronan in the vitreous of patients with rhegmatogenous retinal detachment.","authors":"Birgit Marlies Govers, Bjorn Bakker, Magdalena J de Bruijne, Arie Oosterhof, Elly Versteeg, Anneke I den Hollander, Sander Keijser, B Jeroen Klevering, Willeke F Daamen, T H van Kuppevelt","doi":"10.1016/j.exer.2025.110672","DOIUrl":"https://doi.org/10.1016/j.exer.2025.110672","url":null,"abstract":"<p><strong>Purpose: </strong>To compare hyaluronan (HA) and chondroitin sulfate (CS) concentrations as well as the sulfation pattern of CS domains in the vitreous of rhegmatogenous retinal detachment (RRD) versus non-RRD patients.</p><p><strong>Methods: </strong>Vitreous samples from 56 patients with RRD and 41 patients with floaters, macular hole or epiretinal membranes were collected during pars plana vitrectomy. Disaccharide analysis was performed by high-pressure liquid chromatography (HPLC) to assess HA and CS concentrations in the vitreous and determine CS sulfation.</p><p><strong>Results: </strong>The vitreous of RRD patients showed significantly lower HA concentrations (Mann-Whitney U, p<0.001) and higher CS concentrations (Mann-Whitney U, p<0.001) compared to non-RRD patients. The higher total CS concentration in RRD patients was related to a significant increase in non-sulfated CS domains. The concentration of sulfated CS disaccharides with a 6S domain was significantly decreased in RRD patients compared to non-RRD patients: 4S6S (Mann-Whitney U; p=0.008), 2S6S (Mann-Whitney U; p=0.004), and 6S (Mann-Whitney U; p=0.013). The sulfated CS disaccharides 2S4S, 4S6S, 2S6S, 4S, 2S, and 6S, are significantly more abundant in non-RRD patients.</p><p><strong>Conclusions: </strong>The significant degree of non-sulfated CS domains and decreased HA concentrations in the vitreous of RRD patients could weaken structural organization of the vitreous. Reduced vitreous stability can cause pathological vitreoretinal traction, ultimately leading to rhegmatogenous retinal detachment.</p>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":" ","pages":"110672"},"PeriodicalIF":2.7,"publicationDate":"2025-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145191482","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Promotion of vessel regression by local VEGF-A blockade improves the survival rate of corneal transplants.","authors":"Zhe Chen, Wei Zhang, Mert Mestanoglu, Claus Cursiefen, Felix Bock","doi":"10.1016/j.exer.2025.110652","DOIUrl":"https://doi.org/10.1016/j.exer.2025.110652","url":null,"abstract":"<p><p>To primarily evaluate the efficacy of different topical vascular endothelial growth factor (VEGF) blocking treatments, namely Aflibercept and Bevacizumab, in promoting regression of pathologic corneal neovascularization (NV) and secondarily to investigate their effects on graft survival in a high-risk mouse corneal transplantation model. In addition, the immune modulatory effects were assessed. After 14 days of suture-induced, inflammatory corneal NV, sutures were removed. Anti-VEGF eye drops or vehicle controls were applied topically 3 times daily for one week. After 21 days, the regression of blood vessels (BVs) and lymphatic vessels (LVs) was assessed via immunofluorescence staining. In addition, corneal grafting was performed in another set of mice. Therefore, allogeneic donor corneas from C57BL/6N mice were used and graft survival was monitored weekly for 8 weeks. Finally, hem-and lymphangiogenesis as well as the phenotype of antigen-presenting cells (APCs) in draining lymph nodes (dLNs) and corneas were analyzed by immunohistochemistry and FACS, respectively. Both, Aflibercept and Bevacizumab eye drops supported the regression of both blood and lymphatic vessels. Aflibercept-treated corneas demonstrated decreased APC activation in the dLNs after treatment at day 21. In the high-risk transplantation model, both therapeutics could improve graft survival rates (Aflibercept: 60%, P = 0.0091; Bevacizumab: 50%, P = 0.0547) compared to control (10%). Eight weeks post-transplantation, both treatment arms displayed decreased APC recruitment and an increased expression of Foxp3 on CD4+CD25+ T cells. Our study demonstrates that different topically applied anti-VEGF eye drops effectively reduce pre-existing corneal neovascularization and thereby improve subsequent high-risk corneal transplantation. This translational approach could become a promising strategy to improve the clinical outcome of high risk keratoplasty in patients.</p>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":" ","pages":"110652"},"PeriodicalIF":2.7,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145185153","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Differential TGF-β2 expression in the anterior and posterior eye segments in mice with early streptozotocin-induced diabetes","authors":"Martin Schicht ,&nbsp;Klaus Scholich ,&nbsp;Marco Sisignano ,&nbsp;Gerd Geisslinger ,&nbsp;Friedrich Paulsen ,&nbsp;Elke Lütjen-Drecoll","doi":"10.1016/j.exer.2025.110671","DOIUrl":"10.1016/j.exer.2025.110671","url":null,"abstract":"<div><div>The pathogenesis of diabetic retinopathies (DRs), the main cause of blindness in the population with type 1 or type 2 diabetes, is still poorly understood. In DRs pathology, vascular endothelial growth factor VEGF and transforming growth factor beta (TGF-β) may play a role in disease progression, especially in relation to angiogenesis and inflammation in the retina, respectively. In the present study we investigated expression of TGF-β and VEGF in the anterior and posterior eye segments in streptozotocin-induced diabetic mice (STZ-mice) with an incipient (10 d) and fully developed (20 d) diabetes after injection. In previous studies we have shown that TGF-β2 induces increased formation of extracellular material (ECM) in the outer trabecular meshwork (TM) in the subendothelial region of Schlemm's canal (SC). Therefore, TM and SC as well as the morphology of the scleral and retinal capillaries were investigated using qualitative and quantitative ultrastructural methods. Surprisingly, vascular endothelial cells were morphologically unchanged, and there were no signs of edema. VEGF expression was unchanged in the anterior or posterior segment of the eye. However, we found increased TGF-β2 expression in the anterior segment of the eye, increased ECM in the TM, and thickened basement membranes of the scleral and retinal capillaries. In contrast, decreased TGF-β2 expression was observed in the posterior segment of the eye. These findings suggest that early DR-related changes occur independently of VEGF and highlight the need to further investigate the cell-specific regulation of TGF-β2 in different ocular regions.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"261 ","pages":"Article 110671"},"PeriodicalIF":2.7,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145181932","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hypoxia-driven histone modification landscape and the role of EZH2 in retinal neovascularization","authors":"Yong Lin,&nbsp;Rusen Yang,&nbsp;Tianyi Xu,&nbsp;Juxiu Ye,&nbsp;Hua Zhang,&nbsp;Peter S. Reinach,&nbsp;Jia Qu,&nbsp;Dongsheng Yan","doi":"10.1016/j.exer.2025.110670","DOIUrl":"10.1016/j.exer.2025.110670","url":null,"abstract":"<div><div>Enhancer of zeste homolog 2 (EZH2) is a critical histone methyltransferase involved in catalyzing H3K27 trimethylation, regulating cell fate determination, DNA damage repair, cell proliferation, and differentiation. However, its role in retinal neovascularization (RNV) remains unclear. Here, we investigated the effects of EZH2-mediated H3K27me3 in human retinal microvascular endothelial cells (HRMECs) under hypoxic conditions. Hypoxia significantly upregulated various histone modifications in HRMECs, with the most pronounced increase in H3K27me3. Immunofluorescence confirmed increased EZH2 expression in the neo-vessels of the oxygen-induced retinopathy (OIR) model and hypoxia-treated HRMECs. Inhibition of EZH2, through specific inhibitors or siRNA, effectively reduced EZH2 and H3K27me3 levels, leading to decreased HRMEC proliferation, migration, and angiogenesis. Chromatin immunoprecipitation assays indicated that EZH2-mediated H3K27me3 suppresses miR-221 expression. Overexpression of miR-221 reproduced the effects of EZH2 inhibition, and dual-luciferase reporter assays confirmed that miR-221 directly targets KDR. Inhibition of miR-221 counteracted the KDR downregulation caused by EZH2 inhibition. Furthermore, intravitreal administration of the EZH2 inhibitor DZNeP significantly reduced RNV in OIR mice. In conclusion, our findings identify the EZH2-miR-221-KDR axis as a critical regulatory pathway in RNV and suggest that EZH2 inhibition may represent a promising therapeutic strategy for RNV-related diseases.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"261 ","pages":"Article 110670"},"PeriodicalIF":2.7,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145185198","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comment on “Structural changes in retinal and choroidal vasculature following N-methyl-N- nitrosourea-induced retinal degeneration in rats” by Shimoda et al.","authors":"Ying Wei,&nbsp;Chang He","doi":"10.1016/j.exer.2025.110666","DOIUrl":"10.1016/j.exer.2025.110666","url":null,"abstract":"","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"261 ","pages":"Article 110666"},"PeriodicalIF":2.7,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145174407","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NaIO3-induced RPE toxicity leads to chorioretinal atrophy, scleral remodeling, and myopic axial elongation in mice","authors":"Takafumi Suzuki,&nbsp;Masako Nagahara,&nbsp;Kentaro Hayashi,&nbsp;Tomoyasu Shiraya,&nbsp;Ryo Terao,&nbsp;Megumi Honjo,&nbsp;Takashi Ueta","doi":"10.1016/j.exer.2025.110665","DOIUrl":"10.1016/j.exer.2025.110665","url":null,"abstract":"<div><div>Pathologic myopia, a vision-threatening subtype of myopia, is characterized by axial elongation accompanied by chorioretinal atrophy and scleral remodeling. While lens-induced and form-deprivation myopia models have elucidated the role of visual input in ocular growth, the contribution of retinal pigment epithelium (RPE) and choriocapillaris (CC) damages remains incompletely understood. Here, we employed a sodium iodate (NaIO₃) model—traditionally used in age-related macular degeneration research—to investigate whether the damage to the RPE and CC can induce changes in the sclera and axial length. We demonstrate that systemic NaIO₃ exposure induced widespread RPE and CC degeneration, retinal thinning, and chorioretinal atrophy, all of which were partially rescued by the ferroptosis inhibitor ferrostatin-1 (Fer-1) in mice. These degenerative changes correlated with a significant myopic shift (∼15 D) and axial elongation (∼0.3 mm), alongside scleral thinning, decreased COL1A1 expression, and reduced collagen fibril diameter—hallmarks of scleral extracellular matrix remodeling. Fer-1 treatment attenuated both the anatomical and molecular features of myopia, supporting a causal role of lipid peroxidation in this process. Our findings demonstrate that lipid peroxidation-associated RPE and CC damage can trigger scleral remodeling and axial elongation independent of visual input, providing a novel mechanistic insight into ocular growth regulation. The NaIO₃ model may therefore serve as a unique and reproducible platform for studying chorioretinal degeneration-driven myopia and evaluating lipid peroxidation-targeting therapies.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"261 ","pages":"Article 110665"},"PeriodicalIF":2.7,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145174412","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bimodal ex vivo biomechanical characterization of corneal UVA-crosslinking via optical coherence elastography and nanoindentation under physiological conditions","authors":"Robert Lohmüller ,&nbsp;Matteo Frigelli ,&nbsp;Günther Schlunck ,&nbsp;Sabine Kling ,&nbsp;Phillipe Büchler ,&nbsp;Thomas Reinhard ,&nbsp;Stefan J. Lang","doi":"10.1016/j.exer.2025.110664","DOIUrl":"10.1016/j.exer.2025.110664","url":null,"abstract":"<div><div>Riboflavin-mediated UVA corneal crosslinking (CXL) stabilizes corneal ectasia, but its biomechanical effects remain difficult to quantify. This study combines Optical Coherence Elastography (OCE), an imaging technique which provides spatially resolved deformation maps across the corneal volume, with Nanoindentation (NI), a technique that relies on direct force measurements at predefined locations on the cornea, to assess corneal biomechanics before and after CXL. Ten human donor corneas were incubated for 24 h in a medium containing 15 % dextran to control hydration and thickness. A custom-made sample mount exerting adjustable retrocorneal fluid pressure enabled <em>ex vivo</em> characterization of the entire cornea while maintaining its natural shape and physiological tension. Each cornea was analyzed with both OCE and NI before and after standard Dresden protocol CXL. Linear mixed-effects models revealed significant CXL-induced stiffening across both methods, most pronounced in the central cornea and a decreasing peripherally. OCE showed a central reduction in axial strain (<span><math><mrow><msub><mi>ε</mi><mrow><mi>z</mi><mi>z</mi></mrow></msub></mrow></math></span>) of 2.6 ‰ (p &lt; 0.01), while NI revealed a consistent central increase in Hertz elastic modulus (<span><math><mrow><msub><mi>E</mi><mi>n</mi></msub></mrow></math></span>) of ∼14 kPa (p &lt; 0.01) across both loading rates (300 and 600 μN/min). Although baseline stiffness increased with loading rate (128 kPa vs. 147 kPa), the CXL stiffening effect remained constant. Both techniques confirmed significant regional differences in the CXL response from central to peripheral (p &lt; 0.05). This study provides spatially resolved, quantitative insight into corneal biomechanics using two fundamentally different mechanical testing modalities. The integration of imaging-based OCE with force-based NI establishes a robust experimental foundation for <em>in silico</em> numerical modeling, enabling CXL treatment optimization and predictive simulations.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"261 ","pages":"Article 110664"},"PeriodicalIF":2.7,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145174378","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}