Experimental eye research最新文献

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Olink Proteomics Profiling Reveals Metabolism-Related Protein Biomarkers in Diabetic Retinopathy. Olink蛋白质组学分析揭示糖尿病视网膜病变代谢相关蛋白生物标志物。
IF 3 2区 医学
Experimental eye research Pub Date : 2025-06-19 DOI: 10.1016/j.exer.2025.110495
Qiu-Yang Zhang, Hui-Ying Zhang, Qing Liu, Feng-Sheng Wang, Yue Zhu, Si-Guo Feng, Jin Yao, Biao Yan
{"title":"Olink Proteomics Profiling Reveals Metabolism-Related Protein Biomarkers in Diabetic Retinopathy.","authors":"Qiu-Yang Zhang, Hui-Ying Zhang, Qing Liu, Feng-Sheng Wang, Yue Zhu, Si-Guo Feng, Jin Yao, Biao Yan","doi":"10.1016/j.exer.2025.110495","DOIUrl":"https://doi.org/10.1016/j.exer.2025.110495","url":null,"abstract":"<p><p>Diabetic retinopathy (DR), a major cause of vision loss among working-age adults, represents a microvascular complication of diabetes mellitus that is associated with metabolic dysregulation. This study employed Olink proteomics profiling to identify novel biomarkers and elucidate the potential mechanism of DR. A total of 44 patients with DR and 44 individuals with cataracts serving as controls were enrolled in the study. Aqueous humor samples from all participants were analyzed for 92 metabolism-related proteins using the Olink® Metabolism Panel. Differential expression analysis identified 78 proteins with altered expression between the two groups. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of differentially expressed proteins revealed that the enriched pathways were primarily associated with blood vessel development, cellular signaling, and protein degradation. Notably, TFF2 exhibited exceptional diagnostic potential for DR with an area under the curve (AUC) of 0.9974 in receiver operating characteristic (ROC) analysis. Elevated TFF2 levels were further validated in both DR patients and a streptozotocin (STZ)-induced diabetic murine model. Functional experiments revealed that TFF2 contributed to endothelial angiogenic effects in vitro and retinal vascular dysfunction in vivo. These findings underscore the potential of TFF2 as a diagnostic biomarker for DR and offer new insights into the metabolic pathways driving DR pathogenesis.</p>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":" ","pages":"110495"},"PeriodicalIF":3.0,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144340060","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}
引用次数: 0
Can interventional clinical trials be implemented in intermediate age-related macular degeneration? 介入性临床试验可以在中度年龄相关性黄斑变性中实施吗?
IF 3 2区 医学
Experimental eye research Pub Date : 2025-06-19 DOI: 10.1016/j.exer.2025.110493
Robert P Finger
{"title":"Can interventional clinical trials be implemented in intermediate age-related macular degeneration?","authors":"Robert P Finger","doi":"10.1016/j.exer.2025.110493","DOIUrl":"https://doi.org/10.1016/j.exer.2025.110493","url":null,"abstract":"","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":" ","pages":"110493"},"PeriodicalIF":3.0,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144340059","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}
引用次数: 0
Application of transcriptome sequencing to identify and explore biomarkers in a rat model of optic nerve crush 应用转录组测序鉴定和探索视神经压迫大鼠模型中的生物标志物
IF 3 2区 医学
Experimental eye research Pub Date : 2025-06-18 DOI: 10.1016/j.exer.2025.110494
Sha-sha Yu , Yun Zhao , Xiao-hui Zhou , Hui Zhang , Hai-qiang Yu , Xiao-yong Yuan
{"title":"Application of transcriptome sequencing to identify and explore biomarkers in a rat model of optic nerve crush","authors":"Sha-sha Yu ,&nbsp;Yun Zhao ,&nbsp;Xiao-hui Zhou ,&nbsp;Hui Zhang ,&nbsp;Hai-qiang Yu ,&nbsp;Xiao-yong Yuan","doi":"10.1016/j.exer.2025.110494","DOIUrl":"10.1016/j.exer.2025.110494","url":null,"abstract":"<div><div>Traumatic optic neuropathy (TON) has a profound impact on affected individuals, yet the treatment of TON continues to present significant challenges. In this context, we aimed to explore diagnostic biomarkers and potential mechanisms underlying TON in a rat optic nerve crush (ONC) model via a transcriptomics approach. We extracted total RNA from 32 rat retina samples. First, candidate genes and hub genes were identified. The biomarkers were subsequently identified by random forest (RF) and receiver operating characteristic (ROC) analyses. A nomogram was constructed to assess the diagnostic value of the biomarkers. Finally, functional analysis, subcellular localization analysis, drug prediction, and gene expression verification were performed. IFIT3, IFI44, USP18, ZBP1, IRGM, and OAS1B were identified as biomarkers in the ONC model and exhibited strong diagnostic utility, with all areas under the curve (AUCs) exceeding 0.8. Furthermore, these biomarkers were found to be collectively involved in “cytokine–cytokine receptor interactions”. Subcellular localization analysis revealed the predominant presence of these biomarkers in the cell nucleus and cytoplasm. Moreover, 8 drugs targeting OAS1B and 25 drugs targeting IRGM were predicted. Notably, the shared targeting of lipopolysaccharides, carbon nanotubes, pentachlorophenol, and silver by both OAS1B and IRGM has significant therapeutic potential. Additionally, IFIT3, IFI44, USP18, ZBP1, IRGM, and OAS1B expression levels were markedly elevated in ONC samples compared with control samples, underscoring their relevance as promising biomarkers for ONC. Therefore, we conclude that IFIT3, IFI44, USP18, ZBP1, IRGM, and OAS1B were identified as biomarkers of ONC, providing a potential theoretical basis for ONC related studies.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"258 ","pages":"Article 110494"},"PeriodicalIF":3.0,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144330672","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}
引用次数: 0
Quercetin diminishes scleral ER stress and protein misfolding: High throughput transcriptome analysis in form-deprivation myopia of guinea pigs. 槲皮素减少巩膜内质网应激和蛋白质错误折叠:豚鼠形式剥夺性近视的高通量转录组分析。
IF 3 2区 医学
Experimental eye research Pub Date : 2025-06-18 DOI: 10.1016/j.exer.2025.110485
Lingfeng Lv, Danyang Che, Zewei Zhang, Weijie Zhang, Qimin Zhou, Fang Li, Jibo Zhou
{"title":"Quercetin diminishes scleral ER stress and protein misfolding: High throughput transcriptome analysis in form-deprivation myopia of guinea pigs.","authors":"Lingfeng Lv, Danyang Che, Zewei Zhang, Weijie Zhang, Qimin Zhou, Fang Li, Jibo Zhou","doi":"10.1016/j.exer.2025.110485","DOIUrl":"https://doi.org/10.1016/j.exer.2025.110485","url":null,"abstract":"<p><p>This study aims to verify the involvement of scleral endoplasmic reticulum stress (ERS) in form-deprived myopia (FDM) model of guinea pigs, investigate the therapeutic effects of quercetin (Qcn) on FDM as well as explore the underlying mechanisms in human scleral fibroblast (HSF). Scleral tissue of the right eyes of NC / FDM guinea pigs were collected for RNA-seq. Then, the animals were divided into NC / Qcn / FDM /FDM + Qcn group. After 4 weeks of treatment, qPCR analysis detected mRNA expression of ERS-related genes. Sirius red staining and Tunel staining were performed to observe collagen change and level of apoptosis in sclera. In vitro, HSF was treated with quercetin or tunicamycin (Tm). Western blotting detected expression of ERS-related molecules protein, MMP-2 and COL1A1 protein, while qPCR analysis detected mRNA expression. Level of misfolded protein and GRP78 in HSF were observed by immunofluorescence. The results came out that ERS-related genes GRP78, CHOP, ATF3 and ERS-related pathway were significantly upregulated in FDM eyes according to RNA-seq, which was confirmed by qPCR. Quercetin significantly inhibited FDM progression but did not affect normal refractive and axial development. Quercetin reduced the levels of ERS-related genes in FDM eyes, inhibited apoptosis and restored type I collagen expression. In HSF, quercetin inhibited Tm-induced ERS and reduced the accumulation of misfolded proteins. Our study pioneered the confirmation of the role of scleral ERS in FDM through RNA-seq. Quercetin mitigates FDM, likely by promoting proper protein folding, inhibiting the PERK/ATF3 signaling pathway, and alleviating ERS-induced apoptosis in HSFs.</p>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":" ","pages":"110485"},"PeriodicalIF":3.0,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144336444","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}
引用次数: 0
The m6A transferase METTL3 regulates high glucose-induced proliferation and apoptosis of human lens epithelial cells through the lncRNA TUG1/KHSRP/p38MAPK signaling axis m6A转移酶METTL3通过lncRNA TUG1/KHSRP/p38MAPK信号轴调控高糖诱导的人晶状体上皮细胞增殖和凋亡
IF 3 2区 医学
Experimental eye research Pub Date : 2025-06-18 DOI: 10.1016/j.exer.2025.110492
Yuxuan Li, Ziyi Yao, Xiaoqin Gao, Yaxin Niu, Ziqing Gao, Shengqun Jiang
{"title":"The m6A transferase METTL3 regulates high glucose-induced proliferation and apoptosis of human lens epithelial cells through the lncRNA TUG1/KHSRP/p38MAPK signaling axis","authors":"Yuxuan Li,&nbsp;Ziyi Yao,&nbsp;Xiaoqin Gao,&nbsp;Yaxin Niu,&nbsp;Ziqing Gao,&nbsp;Shengqun Jiang","doi":"10.1016/j.exer.2025.110492","DOIUrl":"10.1016/j.exer.2025.110492","url":null,"abstract":"<div><div>Diabetic cataract (DC) is one of the ocular complications in diabetic patients. This study aimed to investigate the mechanism of Methyltransferase-like 3 (METTL3)/Long non-coding RNA taurine-upregulated gene 1 (lncRNA TUG1)/KH-type splicing regulatory protein (KHSRP)/p38 mitogen-activated protein kinase (p38MAPK) signaling axis in DC progression. The expression of METTL3, TUG1, KHSRP, p38, and apoptosis-related proteins in tissues and cells were detected by RT-qPCR or Western blot. The m6A level was quantified using m6A colorimetric assay. RNA immunoprecipitation (RIP) assay verified the binding between RNA and protein. Proliferation and apoptosis of human lens epithelial cells (HLECs) were analyzed by CCK8 assay and flow cytometry. High glucose (HG) increased METTL3-mediated m6A methylation, which increased TUG1 expression. Knockdown of TUG1 increased HG-induced cell proliferation and decreased apoptosis. Knockdown of TUG1 decreased KHSRP expression, and RIP assays showed that TUG1 bound to KHSRP. Knockdown of KHSRP reversed the decrease in cell proliferation and increase in apoptosis caused by TUG1 expression. KHSRP affects the phosphorylation level of p38 and regulates cell proliferation and apoptosis through the p38MAPK pathway. This suggests that the m6A transferase METTL3 regulates DC proliferation and apoptosis through the lncRNA TUG1/KHSRP/p38MAPK signaling axis, providing a novel target for the treatment of DC.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"258 ","pages":"Article 110492"},"PeriodicalIF":3.0,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144322189","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}
引用次数: 0
TLR4 signal inhibition alleviates alkali-burn induced corneal neovascularization TLR4信号抑制可缓解碱烧伤诱导的角膜新生血管。
IF 3 2区 医学
Experimental eye research Pub Date : 2025-06-15 DOI: 10.1016/j.exer.2025.110486
Cong Xia , Yan Deng , Yichen Lu , Lumei Kang , Xiaojuan Wan , Hongping Chen , Xiaolong Yin
{"title":"TLR4 signal inhibition alleviates alkali-burn induced corneal neovascularization","authors":"Cong Xia ,&nbsp;Yan Deng ,&nbsp;Yichen Lu ,&nbsp;Lumei Kang ,&nbsp;Xiaojuan Wan ,&nbsp;Hongping Chen ,&nbsp;Xiaolong Yin","doi":"10.1016/j.exer.2025.110486","DOIUrl":"10.1016/j.exer.2025.110486","url":null,"abstract":"<div><div>Toll-like receptor 4 (TLR4), recognized as a fundamental mediator of inflammatory signaling, plays a crucial role in orchestrating the inflammatory response. Previous studies suggested that TLR4 knockout (KO) notably reduced corneal vascular areas induced by silver nitrate burn based on the morphological observation. The current study seeks to elucidate the influence of TLR4 signaling on corneal neovascularization (CNV) and to examine the underlying mechanisms. The model of alkali burn (AB)-induced CNV was built using TLR4 KO and wildtype (WT) mice. CNV was detected using a slit lamp. Corneal thickness was evaluated using H&amp;E staining. The expression levels of VEGF-A, MyD88, and NF-κB were evaluated employing Western blot analysis, immunohistochemistry, and Real-time PCR techniques. The inflammation factors, IL-1β, TNF-α, and IL-6, were quantified using Real-time PCR. In addition, Resatorvid (Tak242), a specific inhibitor of TLR4, was used to treat AB cornea of WT mice. AB enhanced TLR4 signaling components, including MyD88 and NF-κB. TLR4 inhibition alleviated AB-induced corneal neovascularization and corneal thickness. The TLR4 signal, inflammatory factors and VEGF-A were also down-regulated. Our data indicated that TLR4 participated in the pathology of AB-induced CNV. TLR4 was over-expressed in the cornea of AB mice. TLR4 inhibition alleviated AB-induced CNV, and suppressed MyD88, NF-κB, VEGF-A, and inflammation factors. These findings may provide new insights for the clinical treatment of AB-induced CNV.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"258 ","pages":"Article 110486"},"PeriodicalIF":3.0,"publicationDate":"2025-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144316258","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}
引用次数: 0
Tailoring UPS-to-autophagy transition to restore RGC prosperity and functionality in a rodent traumatic optic neuropathy model 在啮齿动物创伤性视神经病变模型中,调整ups到自噬的过渡以恢复RGC的繁荣和功能。
IF 3 2区 医学
Experimental eye research Pub Date : 2025-06-14 DOI: 10.1016/j.exer.2025.110489
Ching-Yun Wang , Lawrence Chen , Jia-Ying Chien , Hsin-Yu Ho , Ting-Yi Lin , Shun-Ping Huang
{"title":"Tailoring UPS-to-autophagy transition to restore RGC prosperity and functionality in a rodent traumatic optic neuropathy model","authors":"Ching-Yun Wang ,&nbsp;Lawrence Chen ,&nbsp;Jia-Ying Chien ,&nbsp;Hsin-Yu Ho ,&nbsp;Ting-Yi Lin ,&nbsp;Shun-Ping Huang","doi":"10.1016/j.exer.2025.110489","DOIUrl":"10.1016/j.exer.2025.110489","url":null,"abstract":"<div><div>Direct or indirect injury to the optic nerve can lead to traumatic optic neuropathy (TON), a pathological process eventually resulting in long-term vision loss. Experimentally, optic nerve crush (ONC) simulates TON by inducing retinal ganglion cell (RGC) apoptosis and vision loss. This study investigates the neuroprotective effect of a HECT domain-E3 ubiquitin ligase inhibitor, Compound 056, on retinal ganglion cells after traumatic injury. Experimental traumatic optic neuropathy (TON) was induced by mechanical compression of the rodent optic nerve. Compound 056 was administered (60 mg/kg) subcutaneously once on the same day after TON induction. Compound 056 treatment (60 mg/kg) significantly increased RGC survival and preserved visual function after TON induction. The number of TUNEL-positive cells was significantly decreased, and optic disc edema was reduced. Bulk RNA sequencing revealed that HUWE1, an E3 ubiquitin ligase, was potentially linked to the suspended autophagy and NLRP3-mediated neuroinflammation after TON induction. We demonstrated that compound 056 effectively alleviated neuroinflammation and enhanced autophagic flux at transcriptomic and protein levels. These findings suggest compound 056 may have therapeutic potential in treating TON by modulating NLRP3 inflammasome pathways and the autophagic flux within the retina and optic nerve.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"258 ","pages":"Article 110489"},"PeriodicalIF":3.0,"publicationDate":"2025-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144301456","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}
引用次数: 0
Baicalin ameliorates inflammation response in diabetic dry eye models through the inhibition of the PERK/TXNIP/NLRP3 pathway 黄芩苷通过抑制PERK/TXNIP/NLRP3通路改善糖尿病干眼模型的炎症反应。
IF 3 2区 医学
Experimental eye research Pub Date : 2025-06-13 DOI: 10.1016/j.exer.2025.110487
Ruoqing Wang , Changxia Dong , Ying Chen , Chen Chen , Xinmei Zhao , Xinyang Han , Xia Sun , Xiaowei Sun , Yuanbin Li
{"title":"Baicalin ameliorates inflammation response in diabetic dry eye models through the inhibition of the PERK/TXNIP/NLRP3 pathway","authors":"Ruoqing Wang ,&nbsp;Changxia Dong ,&nbsp;Ying Chen ,&nbsp;Chen Chen ,&nbsp;Xinmei Zhao ,&nbsp;Xinyang Han ,&nbsp;Xia Sun ,&nbsp;Xiaowei Sun ,&nbsp;Yuanbin Li","doi":"10.1016/j.exer.2025.110487","DOIUrl":"10.1016/j.exer.2025.110487","url":null,"abstract":"<div><div>Diabetes mellitus is an important risk factor for dry eye. Dry eye may cause structural and functional disorders in corneal epithelial cells, seriously affecting the visual quality of diabetic patients. Baicalin (BA), a constituent of Scutellariae baicalensis, has anti-inflammatory and antioxidant properties. However, whether BA exerts a therapeutic effect on patients with diabetic dry eye and the underlying mechanism are unclear. Here, we explored the underlying mechanism of baicalin in diabetic dry eye. In cells, we used high glucose-stimulated human corneal epithelial (HCE-T) cells for modeling. There were differences in the expression of the pathway-related proteins p-PERK, NLRP3, TXNIP, and IL-1β under different glucose concentrations, and the highest expression of relevant proteins was observed with 25 mmol/L glucose. BA protected against high glucose-induced HCE-T-cell injury and apoptosis. In addition, BA inhibited the PERK/TXNIP/NLRP3 axis and thus attenuated the inflammatory response of HCT-T cells, but the effect that was reversed by the PERK agonist CCT020312. We used C57BL/6 mice injected intraperitoneally with streptozotocin (STZ) to establish the animal model. BA suppressed the PERK/TXNIP/NLRP3 pathway and ameliorated corneal inflammation in diabetic dry eye model mice. Moreover, BA increased tear secretion and decreased corneal fluorescence scores in diabetic dry eye model mice. Thus, our study demonstrates the important value of BA in alleviating diabetic dry eye and provides new insights into the development of diabetic dry eye.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"258 ","pages":"Article 110487"},"PeriodicalIF":3.0,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144301455","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}
引用次数: 0
The kallikrein kinin system alters neuroretinal and visual responses in mice 激肽激肽系统改变小鼠的神经视网膜和视觉反应
IF 3 2区 医学
Experimental eye research Pub Date : 2025-06-10 DOI: 10.1016/j.exer.2025.110484
Allen Clermont , Nivetha Murugesan , Cheng-Mao Lin , David Antonetti , Lloyd P. Aiello , Edward P. Feener
{"title":"The kallikrein kinin system alters neuroretinal and visual responses in mice","authors":"Allen Clermont ,&nbsp;Nivetha Murugesan ,&nbsp;Cheng-Mao Lin ,&nbsp;David Antonetti ,&nbsp;Lloyd P. Aiello ,&nbsp;Edward P. Feener","doi":"10.1016/j.exer.2025.110484","DOIUrl":"10.1016/j.exer.2025.110484","url":null,"abstract":"<div><div>The kallikrein-kinin system (KKS) has been implicated in mediating both VEGF-dependent and VEGF-independent retinal vascular dysfunction and edema; however, little is known about the effect of the KKS on neuroretinal function. This study investigates the effects of bradykinin (BK) and Factor XIIa (FXIIa), an activator of the KKS, on visual function in mice. Intravitreal injection (IVI) of BK decreased optokinetic spatial frequency by 23 %, 20 % and 14 % (p &lt; 0.001) at 6, 12 and 24 h, respectively. IVI of BK increased scotopic electroretinogram (ERG) a-wave amplitudes by 38 % and b-wave by 40 % (p &lt; 0.01) measured at 24 h post injection. IVI of FXIIa increased scotopic ERG a- and b-wave amplitudes by 44 % and 51 % at 24 h post injection. IVI of VEGF increased scotopic a-wave and b-wave amplitudes by 67 % and 71 % (p &lt; 0.001) compared to PBS in wild type (WT) but did not significantly alter the scotopic ERG responses in FXII deficient (FXII<sup>−/−</sup>) mice. Pretreatment of WT mice with an oral FXIIa inhibitor, KV998086, reduced the VEGF-induced increase in a-wave amplitude by 99 % (p &lt; 0.001) and b-wave by 90 % (p &lt; 0.01). In summary, this study demonstrates that the KKS alters neuroretinal and visual response in mice. FXIIa inhibition may protect from VEGF-induced visual dysfunction that is mediated by the KKS.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"258 ","pages":"Article 110484"},"PeriodicalIF":3.0,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144280382","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}
引用次数: 0
In vivo changes in the gradient of refractive index distribution in the accommodating human lens 体内调节人体晶状体中折射率分布梯度的变化
IF 3 2区 医学
Experimental eye research Pub Date : 2025-06-10 DOI: 10.1016/j.exer.2025.110483
Alyssa L. Lie , Xingzheng Pan , Thomas W. White , Paul J. Donaldson
{"title":"In vivo changes in the gradient of refractive index distribution in the accommodating human lens","authors":"Alyssa L. Lie ,&nbsp;Xingzheng Pan ,&nbsp;Thomas W. White ,&nbsp;Paul J. Donaldson","doi":"10.1016/j.exer.2025.110483","DOIUrl":"10.1016/j.exer.2025.110483","url":null,"abstract":"<div><div>Previously, we observed that accommodative rounding of the young human lens was accompanied by a redistribution in its internal free water content that resulted in a more linear water gradient across the anterior region of the lens. We hypothesised that this would produce a smoother gradient of refractive index (GRIN) which would, in turn, increase the internal lens refractive contribution to lens power during accommodation. However, <em>in vivo</em> studies of the human lens GRIN changes during accommodation remain limited and report mixed findings. To gain further insight into this, we employed our established magnetic resonance imaging (MRI) protocols to measure the changes in lens geometry and GRIN for 10 young (aged 20–27 years) and 14 middle-aged (aged 48–55 years) adults under a 3 Dioptre (D) accommodative stimulus. The MRI-derived lens measurements were then modelled in Zemax OpticStudio software to quantify the refractive contribution of the GRIN changes to the overall lens power increase during accommodation. In young participants, we observed a significant smoothing of the anterior GRIN, which contributed some 1.47–1.59 D of the total 3.04 D increase in lens power under the 3 D accommodative stimulus. In contrast, presbyopic lenses showed no significant changes in geometry or GRIN, culminating in only a total 0.62 D increase in lens power. These findings support the presence of an intracapsular mechanism of accommodation (ICMA) and highlight the need to consider internal lens optics alongside mechanical properties when developing new treatments for presbyopia.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"258 ","pages":"Article 110483"},"PeriodicalIF":3.0,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144280271","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}
引用次数: 0
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