Experimental eye research最新文献_第3页

Interactions of choroid and sclera in the myopia model of the chicken 鸡近视模型中脉络膜与巩膜的相互作用。

IF 2.7 2区医学 Q1 OPHTHALMOLOGY

Experimental eye research

Pub Date : 2026-02-04 DOI: 10.1016/j.exer.2026.110904

Ute Mathis , Gustav Christensen , Marita Feldkaemper , Falk Schroedl , Alexandra Kaser-Eichberger , Frank Schaeffel

Purpose

Changes in choroidal thickness are currently used to predict future refractive error development but there is incomplete knowledge about the communication between choroid and sclera. We studied how choroidal thickness changes interact with scleral thickness changes and how the abundance of dopamine (DA)- and all-trans retinoic acid (atRA)-synthetizing choroidal cells varies when choroidal thickness is altered by drugs.

Methods

Changes in choroidal thickness were induced by a single intravitreal injection in the morning of the muscarinic antagonist atropine, the DA agonist apomorphine or the DA antagonist spiperone. Thickness of the choroid and the scleral layers was measured by spectral domain optical coherence tomography (SD-OCT). Immunocytochemistry was used to study the distribution of dopamine-synthetizing structures in the choroid and their colocalisation with retinaldehyde dehydrogenase 2 (RADLH2), the key synthetizing enzyme of atRA.

Results

(1) Both atropine and apomorphine increased choroidal thickness over the day while spiperone resulted in a decrease. (2) For apomorphine and spiperone, choroidal thickness changes were positively correlated with thickness changes in both the cartilaginous and fibrous layers of the sclera. With atropine, only the cartilaginous layer thickened. (3) DA was co-localized with RALDH2 in stromal cells in the choroid in a few cases but the numbers of double-stained cells increased massively after drug injections. (4) RALDH2-immunoreactivity (indicating atRA activity) increased, no matter whether the choroid and the sclera thickened or thinned.

Conclusions

Following drug injections, thickness changes of choroid and sclera were correlated and occurred without phase delay. Numbers of DA and RALDH2 co-expressing cells in the choroid increased. Choroidal dopaminergic cells that synthesize atRA appear to act as activators of scleral metabolic activity during both scleral growth stimulation and inhibition.

目的：脉络膜厚度的变化目前被用来预测未来屈光不正的发展，但对脉络膜和巩膜之间的联系尚不完全了解。我们研究了脉络膜厚度变化如何与巩膜厚度变化相互作用，以及当药物改变脉络膜厚度时，合成多巴胺（DA）和全反式维甲酸（atRA）的脉络膜细胞的丰度如何变化。方法：早晨单次玻璃体内注射毒蕈碱拮抗剂阿托品、DA激动剂阿波啡或DA拮抗剂spiperone诱导脉络膜厚度变化。采用光谱域光学相干断层扫描（SD-OCT）测量脉络膜和巩膜层厚度。利用免疫细胞化学方法研究了多巴胺合成结构在脉络膜中的分布及其与atRA合成关键酶视黄醛脱氢酶2 （RADLH2）的共定位。结果：(1)阿托品和阿波啡均使脉络膜厚度增加，而螺泼酮使脉络膜厚度减少。(2)阿扑啡和spiperone的巩膜厚度变化与巩膜软骨层和纤维层厚度变化均呈正相关。使用阿托品，只有软骨层增厚。(3)少数病例中DA与RALDH2在脉络膜基质细胞中共定位，但注射药物后双染细胞数量大量增加。(4)无论脉络膜和巩膜增厚或变薄，raldh2免疫反应性（表明atRA活性）均升高。结论：药物注射后脉络膜与巩膜厚度变化具有相关性，且无相延迟。脉络膜中DA和RALDH2共表达细胞数量增加。合成atRA的脉络膜多巴胺能细胞似乎在巩膜生长刺激和抑制过程中作为巩膜代谢活性的激活剂。

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引用次数: 0

Visual stimulation enhances retrograde transport of BDNF from the superior colliculus to the retina in health and autoimmune uveitis 在健康和自身免疫性葡萄膜炎中，视觉刺激增强BDNF从上丘向视网膜的逆行运输。

IF 2.7 2区医学 Q1 OPHTHALMOLOGY

Experimental eye research

Pub Date : 2026-02-04 DOI: 10.1016/j.exer.2026.110906

Miloslav Zloh , Patrik Kutilek , Andrea Stofkova

Experimental autoimmune uveoretinitis (EAU) shows degeneration of retinal neurons, including retinal ganglion cells (RGCs), already in its early phase. Based on our previous study demonstrating the attenuation of EAU by brain-derived neurotrophic factor (BDNF), whose retinal levels were increased by visual stimulation (VS), this study evaluated the effect of VS on BDNF protein expression in brain visual centers, its retrograde transport to the retina, and RGC survival in healthy and EAU mice. 14-day VS increased BDNF expression in the superior colliculus (SC) but not in the lateral geniculate nucleus and primary visual cortex in healthy and EAU mice compared to their unstimulated groups. Furthermore, VS increased numbers of BDNF-positive neurons and astrocytes in the retinorecipient superficial SC (sSC) in healthy and EAU mice, although stimulated EAU mice showed a modest reduction in BDNF-positive neurons compared to stimulated healthy mice. In contrast, unstimulated EAU mice exhibited a marked loss of sSC BDNF-positive neurons and astrocytes compared to unstimulated healthy mice. Additionally, VS promoted retrograde axonal transport of fluorescently labeled BDNF from the sSC to the retina, where it was detected in RGCs, inner retinal neurons, and Müller cells (MCs). These results suggest that VS-induced increases in BDNF expression in the sSC and its retrograde transport to the retina may directly affect multiple types of retinal neurons and MCs, on which BDNF can exert neurotrophic and protective effects. The overall attenuation of EAU histopathology and retinal inflammation, along with improved survival of RGCs in VS-treated EAU mice, is consistent with this suggestion.

实验性自身免疫性葡萄膜视网膜炎（EAU）显示视网膜神经元变性，包括视网膜神经节细胞（RGCs），已经处于早期阶段。基于我们之前的研究表明脑源性神经营养因子（BDNF）对EAU的衰减作用，其视网膜水平在视觉刺激（VS）下升高，本研究评估了VS对健康和EAU小鼠脑视觉中心BDNF蛋白表达、向视网膜逆行转运以及RGC存活的影响。与未刺激组相比，14天VS增加了健康小鼠和EAU小鼠上丘（SC）的BDNF表达，但在外侧膝状核和初级视觉皮层中没有。此外，VS增加了健康小鼠和EAU小鼠视网膜受体浅表SC （sSC）中bdnf阳性神经元和星形胶质细胞的数量，尽管与受刺激的健康小鼠相比，受刺激的EAU小鼠显示出bdnf阳性神经元的适度减少。相反，与未刺激的健康小鼠相比，未刺激的EAU小鼠表现出sSC bdnf阳性神经元和星形胶质细胞的明显损失。此外，VS促进了荧光标记的BDNF从sSC向视网膜的轴突逆行运输，在RGCs、视网膜内神经元和突触细胞（MCs）中检测到它。这些结果表明，vs诱导的BDNF在sSC中的表达增加及其向视网膜的逆行转运可能直接影响多种类型的视网膜神经元和MCs， BDNF可对其发挥神经营养和保护作用。在vs治疗的EAU小鼠中，EAU组织病理学和视网膜炎症的总体衰减以及RGCs的生存改善与这一建议一致。

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引用次数: 0

Modified Autologous Conditioned Serum (mACS) demonstrates the neuroprotective effect in the Benzalkonium chloride (BAK)-induced murine dry eye model 改良的自体条件血清（mACS）在苯扎氯铵（BAK）诱导的小鼠干眼模型中显示出神经保护作用。

IF 2.7 2区医学 Q1 OPHTHALMOLOGY

Experimental eye research

Pub Date : 2026-02-04 DOI: 10.1016/j.exer.2026.110898

En-Chia Mai , Kuo-Hsuan Hung , Shao-Hsuan Chang , Chun Hsiung , Chung-Chuan Hsiung , Lung-Kun Yeh

The purpose of this study was to analyze and compare cytokine and growth factor levels in modified autologous conditioned serum (mACS) and autologous serum (AS) and to evaluate their therapeutic effects in a benzalkonium chloride (BAK)-induced murine dry eye model. Serum samples were obtained from twenty healthy volunteers and analyzed by ELISA. A dry eye model was established in twenty-four C57BL/6 mice by topical application of 0.2% BAK twice daily for seven days. The mice were evenly divided into three subgroups: saline-treated, 0.5% AS-treated, and 0.5% mACS-treated. The right eyes were treated, and the left eyes served as untreated controls. Eyeballs were harvested on days 7 and 14 for immunofluorescence staining. Results showed that neuroprotective factors (BDNF and fractalkine), pro-inflammatory cytokines (IL-1β, IL-6, MIF, TNF-α), and VEGF-A were significantly elevated in the mACS group, whereas PDGF-BB was significantly reduced. Furthermore, immunofluorescence analysis demonstrated a significantly greater recovery of central corneal nerve fibers in the mACS-treated group compared with the saline group at day 7 (p < 0.01).

At day 14, the mACS-treated group continued to show a trend toward increased central corneal nerve regeneration, although this difference did not reach conventional statistical significance (p < 0.1). No significant differences were observed between the AS- and saline-treated groups. In conclusion, compared with AS, mACS demonstrates a cytokine profile suggestive of enhanced neuroprotective potential and may facilitate corneal nerve regeneration in the BAK-induced murine dry eye model.

本研究的目的是分析和比较改良的自体条件血清（mACS）和自体血清（AS）的细胞因子和生长因子水平，并评价它们在苯扎氯铵（BAK）诱导的小鼠干眼模型中的治疗作用。采集20名健康志愿者血清，采用ELISA法进行分析。以24只C57BL/6小鼠为实验对象，每日2次外用0.2% BAK，连续7 d建立干眼模型。将小鼠平均分为三个亚组：盐水组、0.5% as组和0.5% macs组。右眼接受治疗，左眼作为未治疗的对照组。第7天和第14天取眼球进行免疫荧光染色。结果显示，mACS组神经保护因子（BDNF和fractalkine）、促炎因子（IL-1β、IL-6、MIF、TNF-α）和VEGF-A显著升高，PDGF-BB显著降低。此外，免疫荧光分析显示，与生理盐水组相比，macs治疗组在第7天角膜中央神经纤维的恢复明显更大（p < 0.01）。在第14天，macs治疗组继续表现出角膜中央神经再生增加的趋势，尽管这种差异没有达到常规统计学意义（p < 0.1）。AS-和盐处理组之间无显著差异。综上所述，与AS相比，mACS显示出增强神经保护潜能的细胞因子谱，并可能促进bac诱导的小鼠干眼模型的角膜神经再生。

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引用次数: 0

Viral microRNA inhibition enhances antiviral immunity by modulating corneal inflammatory and resolution pathways in HSV-1 induced keratitis 病毒microRNA抑制通过调节HSV-1诱导角膜炎的角膜炎症和消退途径增强抗病毒免疫。

IF 2.7 2区医学 Q1 OPHTHALMOLOGY

Experimental eye research

Pub Date : 2026-02-04 DOI: 10.1016/j.exer.2026.110903

Chandrashekhar D. Patil , Raza Ali Naqvi , Araceli Valverde , Hemant Borase , Afsar R. Naqvi , Deepak Shukla

Herpes simplex virus type 1 (HSV-1) is a leading cause of infectious corneal blindness worldwide. Viral persistence and disease severity are strongly influenced by the virus's ability to modulate host immune responses; however, the mechanisms by which HSV-1 alters corneal immunity are incompletely understood. In particular, the role of virus-encoded microRNAs (v-miRs) in shaping corneal immune responses during herpes simplex infection remains unclear. We previosuly showed that inhibition of selected HSV-1 v-miRs reduced viral replication and disease severity in a mouse model of ocular infection. Building on these findings, the present study investigated how v-miR inhibition affects corneal immune responses. Using corneal tissue RNA from HSV-1-infected mice, we performed an immune profiling PCR array by analyzing the expression of 88 genes associated with immune cell markers and polarization states. Topical inhibition of miR-H1-5p, miR-H3-3p, and miR-H6-3p resulted in distinct patterns of immune gene expression compared with the control treatment. Inhibition of these v-miRs altered 16, 31, and 57 immune-related genes, respectively, spanning both myeloid- and lymphoid-associated pathways. Notably, the anti-inflammatory genes Arg1 and Il10 were consistently upregulated across all v-miR inhibitor-treated groups. In parallel, increased expression of the pro-resolution enzymes 15-lox and Alox5 suggested enhanced engagement of resolution pathways. Mechanistic studies demonstrated that v-miRs directly target immune regulatory genes through binding sites within their untranslated regions. Together, these findings suggest that HSV-1 v-miRs contribute to corneal immunopathology by suppressing anti-inflammatory and pro-resolving immune pathways, and that targeted inhibition of v-miRs may promote immune resolution during HSV-1–induced keratitis.

1型单纯疱疹病毒（HSV-1）是全世界传染性角膜失明的主要原因。病毒的持久性和疾病严重程度受到病毒调节宿主免疫反应能力的强烈影响；然而，单纯疱疹病毒-1改变角膜免疫的机制仍不完全清楚。特别是，在单纯疱疹感染期间，病毒编码的microrna （v-miRs）在形成角膜免疫反应中的作用尚不清楚。在先前的一项研究中，抑制选定的HSV-1 v-miRs可降低眼部感染小鼠模型中的病毒复制和疾病严重程度。基于这些发现，本研究探讨了v-miR抑制如何影响角膜免疫反应。利用hsv -1感染小鼠的角膜组织RNA，我们通过分析88个与免疫细胞标记和极化状态相关的基因的表达，建立了免疫谱PCR阵列。与对照处理相比，局部抑制miR-H1-5p、miR-H3-3p和miR-H6-3p导致免疫基因表达模式不同。这些v-miRs的抑制分别改变了16、31和57个免疫相关基因，跨越髓细胞和淋巴细胞相关途径。值得注意的是，抗炎基因Arg1和Il10在所有v-miR抑制剂处理组中一致上调。同时，促分解酶15-lox和Alox5的表达增加表明分解途径的参与增强。机制研究表明，v-miRs通过非翻译区域内的结合位点直接靶向免疫调节基因。总之，这些研究结果表明，单纯疱疹病毒-1型v-miRs通过抑制抗炎和促溶解免疫途径参与角膜免疫病理，并且在单纯疱疹病毒-1诱导的角膜炎期间，靶向抑制v-miRs可能促进免疫溶解。

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引用次数: 0

Apigenin attenuates LPS-induced corneal inflammation by modulating NF-κB and JNK/ERK signaling pathways 芹菜素通过调节NF-κB和JNK/ERK信号通路减轻lps诱导的角膜炎症。

IF 2.7 2区医学 Q1 OPHTHALMOLOGY

Experimental eye research

Pub Date : 2026-02-04 DOI: 10.1016/j.exer.2026.110900

Jiaqi Lin, Sihao Liu, Xiuping Liu, Jiayi Zheng, Yucheng Wang, Ziyan Chen, Kaili Wu

Objective

To investigate the protective effects and molecular mechanisms of apigenin (API) on lipopolysaccharide (LPS)-induced corneal inflammation.

Methods

Immortalized human corneal epithelial cell line (HCECs) and primary human corneal epithelial cells (PHCECs) were used to establish LPS-induced inflammation models in vitro. IL-6 and IL-8 mRNA and protein levels were assessed by qRT-PCR and ELISA. Transcriptome sequencing and KEGG/GO enrichment analyses were performed to identify key pathways. Western blotting evaluated the activation of MAPK (ERK, JNK, P38) and NF-κB (P65, IκBα) pathway proteins, and immunofluorescence was used to examine P65 nuclear translocation. Furthermore, following the establishment of an inflammation model via intrastromal LPS injection in mice, API was administered to assess its impact on ocular inflammation and pro-inflammatory cytokine expression.

Results

API significantly suppressed the expression and secretion of key pro-inflammatory mediators in LPS-stimulated corneal epithelial cells including IL-6, IL-8, and COX2. Transcriptomic analysis confirmed the MAPK and NF-κB pathways as critical components in API'a anti-inflammatory action. API inhibited the phosphorylation of key proteins in the MAPK-JNK/ERK and NF-κB signaling pathways, blocked the nuclear translocation of P65. In mice, API alleviated corneal edema and inflammatory cell infiltration and decreased IL-6 and TNF-α levels in corneal tissue.

Conclusion

API effectively attenuates LPS-induced corneal inflammation by inhibiting JNK/ERK and NF-κB signaling pathways and downstream effectors, thereby reducing the production of pro-inflammatory cytokines such as IL-6, IL-8, COX2, and TNF-α.

目的：探讨芹菜素（API）对脂多糖（LPS）诱导的角膜炎症的保护作用及其分子机制。方法：采用永生化人角膜上皮细胞（HCECs）和原代人角膜上皮细胞（PHCECs）建立lps诱导的体外炎症模型。采用qRT-PCR和ELISA检测IL-6、IL-8 mRNA和蛋白表达水平。转录组测序和KEGG/GO富集分析确定了关键途径。Western blotting检测MAPK （ERK、JNK、P38）和NF-κB （P65、i -κB α）通路蛋白的激活情况，免疫荧光检测P65核易位。此外，通过小鼠眼内脂多糖注射建立炎症模型后，给药API以评估其对眼部炎症和促炎细胞因子表达的影响。结果：API显著抑制lps刺激的角膜上皮细胞中IL-6、IL-8、COX-2等关键促炎介质的表达和分泌。转录组学分析证实MAPK和NF-κB通路是其抗炎作用的关键成分。API抑制MAPK-JNK/ERK和NF-κB信号通路关键蛋白的磷酸化，阻断P65的核易位。API可减轻小鼠角膜水肿和炎症细胞浸润，降低角膜组织中IL-6和TNF-α水平。结论：API通过抑制JNK/ERK和NF-κB信号通路及其下游效应物，从而减少IL-6、IL-8、TNF-α等促炎细胞因子的产生，有效减轻lps诱导的角膜炎症。

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引用次数: 0

Dual-target recombinase polymerase amplification-lateral flow strip (RPA-LFS) for rapid detection of HSV-1 and Fusarium keratoplasticum in infectious keratitis 双靶重组酶聚合酶扩增-横向流动条带（RPA-LFS）快速检测感染性角膜炎HSV-1和角化镰刀菌。

IF 2.7 2区医学 Q1 OPHTHALMOLOGY

Experimental eye research

Pub Date : 2026-02-04 DOI: 10.1016/j.exer.2026.110897

Zehua Chen , Yuting Gu , Chunyan Xue, Rui Wang, Jie Wu

This study focuses on the challenge of pathogen detection in keratitis, aiming to develop a dual target detection strip using recombinant enzyme polymerase amplification (RPA) combined with lateral chromatography strip (LFS) technology, and to detect the specific DNA sequences of Herpes simplex virus type 1 (HSV-1) and Fusarium keratoplasticum (F. keratoplasticum). To test the detection system in different ocular surface samples for keratitis pathogens diagnosis. The RPA primers with good specificity for HSV-1 and F. keratoplasticum were designed and screened separately, and further modified into probes for a dual target RPA-LFS detection system. This LFS test strip can simultaneously detect HSV-1 and F. keratoplasticum, and distinguish them by the positive bands at different test lines. The detection limit of this test strip for two targets is 203.69 copies/reaction for HSV-1 and 84.91 copies/reaction for F. keratoplasticum. There is no cross reactivity with DNA of other common pathogenic microorganisms of ocular surface except for Candida albicans. In clinical sample testing, the dual target detection system has shown reliable detection performance for both eye swaps and cornea tissue. The dual targets RPA-LFS detection system in this study could be completed within 20 min with visualized results, the coincidence rate with qPCR was 93.3%, indicating its broad clinical application prospects for the clinical diagnosis and treatment of infectious keratitis.

本研究针对角膜炎病原体检测面临的挑战，旨在利用重组酶聚合酶扩增（RPA）结合横向色谱条带（LFS）技术开发一种双靶点检测条带，检测单纯疱疹病毒1型（HSV-1）和角化镰刀菌（F. keratoplasticum）的特异性DNA序列。试验检测系统在不同眼表样本中对角膜炎病原菌的诊断价值。分别设计筛选特异性较好的HSV-1和角化F.的RPA引物，并进一步修饰成双靶点RPA- lfs检测系统的探针。该LFS试纸条可同时检测HSV-1和角膜成型F.，并可通过不同检测品系的阳性条带进行区分。该试纸条对1型单纯疱疹病毒的检出限为203.69拷贝/次，对角膜变形F.的检出限为84.91拷贝/次。除白色念珠菌外，与眼表其他常见病原微生物DNA无交叉反应性。在临床样品测试中，双靶标检测系统对换眼和角膜组织均表现出可靠的检测性能。本研究双靶点RPA-LFS检测系统可在20分钟内完成，结果可视化，与qPCR符合率为93.3%，在感染性角膜炎的临床诊断和治疗中具有广阔的临床应用前景。

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引用次数: 0

Predictive value of tear lipidomics biomarkers for TAO activity and relationship with clinical characteristics 泪脂组学标志物对TAO活性的预测价值及其与临床特征的关系。

IF 2.7 2区医学 Q1 OPHTHALMOLOGY

Experimental eye research

Pub Date : 2026-02-03 DOI: 10.1016/j.exer.2026.110901

Xiaofang Wang , Zhiyuan Zhang , Huihui Wu , Yinru Wang , Mengru Su , Xinghong Sun

The objective of this study was to explore the lipid metabolic changes in the active thyroid-associated ophthalmopathy (TAO) through tear lipidomics analysis, screen for biomarkers related to disease activity, and analyze their correlation with clinical features. The study included 32 patients with active TAO and 30 patients with inactive TAO. Liquid chromatography-mass spectrometry (LC-MS) was used to perform lipidomics analysis on tear samples to identify differential lipid molecules. Multivariate statistical analyses, including principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA), were conducted, and machine learning algorithms were employed to evaluate the predictive ability of lipid biomarkers. Additionally, clinical characteristics and blood indicators of the patients were collected to analyze their correlation with the lipid biomarkers. The study identified 247 significantly different lipids in the tears of patients with active TAO, of which 104 were upregulated, mainly involving sphingolipids, glycerophospholipids, and glycerolipids. Through machine learning, four lipids (BisMePA(36:6e), MGMG(38:0), PC(38:3), SM(d38:1)) were selected, which showed good predictive ability for TAO activity (AUC >0.8 for all). Moreover, these lipids were significantly correlated with blood lipid indicators, exophthalmos degree, Schirmer I test, and the area of the foveal avascular zone (FAZ) of the retina. This tear lipidomics analysis provides a new approach for screening biomarkers in the active phase of TAO. The identified lipid biomarkers are significantly correlated with clinical features and have potential clinical application value.

本研究旨在通过泪液脂质组学分析，探讨活动性甲状腺相关眼病（TAO）患者的脂质代谢变化，筛选与疾病活动性相关的生物标志物，并分析其与临床特征的相关性。该研究包括32例活动性TAO患者和30例非活动性TAO患者。采用液相色谱-质谱联用（LC-MS）对泪液样品进行脂质组学分析，鉴别不同的脂质分子。进行多元统计分析，包括主成分分析（PCA）和偏最小二乘判别分析（PLS-DA），并采用机器学习算法评估脂质生物标志物的预测能力。收集患者的临床特征和血液指标，分析其与脂质生物标志物的相关性。本研究发现活跃TAO患者泪液中有247种脂质存在显著差异，其中有104种脂质上调，主要涉及鞘脂、甘油磷脂和甘油脂。通过机器学习筛选出4种脂质(BisMePA（36:6e）、MGMG（38:0）、PC（38:3）、SM(d38:1)，对TAO活性具有较好的预测能力（AUC均为>.8）。血脂与血脂指标、眼球突出度、Schirmer I试验、视网膜中央凹无血管区（FAZ）面积有显著相关性。这种泪液脂质组学分析为TAO活动期生物标志物的筛选提供了一种新的方法。所鉴定的脂质生物标志物与临床特征显著相关，具有潜在的临床应用价值。

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引用次数: 0

Topical insulin for corneal wound healing: Interpreting stromal remodeling endpoints 外用胰岛素治疗角膜创面愈合：解释基质重塑终点：回复：“外用胰岛素对角膜创面愈合的再生作用：从表面恢复到基质重塑。”

IF 2.7 2区医学 Q1 OPHTHALMOLOGY

Experimental eye research

Pub Date : 2026-02-03 DOI: 10.1016/j.exer.2026.110902

Henry Bair

引用次数: 0

PIKfyve is an essential component of the endolysosomal pathway within photoreceptors and the retinal pigment epithelium PIKfyve是光感受器和视网膜色素上皮内溶酶体途径的重要组成部分。

IF 2.7 2区医学 Q1 OPHTHALMOLOGY

Experimental eye research

Pub Date : 2026-02-03 DOI: 10.1016/j.exer.2026.110905

Karen Attia , Ifrah Anjum , Susanne Lingrell , Chavy Dworkind , Matthew D. Benson , Ian M. MacDonald , Jennifer C. Hocking

Phosphoinositides (PIs) are a family of seven low abundance membrane lipids, each with distinct signaling functions. The phosphoinositide kinase PIKfyve generates phosphoinositide-3,5-bisphosphate (PI(3,5)P₂) and PI5P. Emerging evidence implicates PIKfyve in key cellular processes, including autophagy, phagocytosis, endosomal trafficking, lysosomal maintenance, and melanosome formation. Complete loss of PIKfyve function is embryonic lethal in model organisms. In humans, heterozygous mutations in PIKFYVE are associated with Fleck corneal dystrophy and congenital cataracts. In this study, we investigate the role of PIKfyve in photoreceptors and the adjacent retinal pigment epithelium (RPE), host to dynamic endolysosomal pathways required for enduring the high oxidative stress environment, transporting metabolites and phototransduction components, and the breakdown of outer segment discs. To assess PIKfyve function in the retina and RPE in our zebrafish model, we employed CRISPR/Cas9-mediated gene editing and pharmacological inhibition using the specific PIKfyve inhibitor apilimod. Loss of PIKfyve activity leads to RPE expansion characterized by the accumulation of LC3- and LAMP1-positive vacuoles, along with defects in phagosome degradation and minor changes to melanosome biogenesis. Photoreceptors deprived of PIKfyve function develop a single large vacuole in the inner segment, while the OS remains largely intact over the timespan analyzed. Electroretinography (ERG) recordings revealed complete visual impairment in pikfyve crispant larvae and significantly reduced visual function in larvae treated with apilimod post embryogenesis. These findings highlight the critical role of PIKfyve in the development and homeostasis of the RPE and retina.

磷酸肌苷（pi）是一个由7个低丰度膜脂组成的家族，每一个都具有不同的信号功能。磷酸肌苷激酶PIKfyve产生磷酸肌苷-3,5-二磷酸（PI(3,5)P2）和PI5P。新出现的证据表明，PIKfyve参与关键的细胞过程，包括自噬、吞噬、内体运输、溶酶体维持和黑素小体的形成。在模式生物中，完全丧失PIKfyve功能是胚胎致命的。在人类中，PIKFYVE的杂合突变与Fleck角膜营养不良和先天性白内障有关。在这项研究中，我们研究了PIKfyve在光感受器和邻近的视网膜色素上皮（RPE）中的作用，RPE是承受高氧化应激环境所需的动态内溶酶体途径的宿主，运输代谢物和光转导成分，以及外节椎间盘的破坏。为了在我们的斑马鱼模型中评估PIKfyve在视网膜和RPE中的功能，我们使用CRISPR/ cas9介导的基因编辑和特异性PIKfyve抑制剂apilimod的药理抑制。PIKfyve活性的丧失导致RPE扩张，其特征是LC3-和lamp1阳性液泡的积累，以及吞噬体降解缺陷和黑素小体生物发生的微小变化。被剥夺PIKfyve功能的光感受器在内节段形成一个大液泡，而在分析的时间范围内，OS基本保持完整。视网膜电图（ERG）记录显示，pikfyve脆化幼虫完全视力受损，胚胎发生后apilimod处理的幼虫视觉功能显著降低。这些发现强调了PIKfyve在RPE和视网膜的发育和稳态中的关键作用。

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引用次数: 0

Proteomic analysis of corneal epithelial cells in patients with neurotrophic keratopathy 神经营养性角膜病变患者角膜上皮细胞的蛋白质组学分析。

IF 2.7 2区医学 Q1 OPHTHALMOLOGY

Experimental eye research

Pub Date : 2026-01-31 DOI: 10.1016/j.exer.2026.110899

Jiarong Luo , Wentao Han , Shaohua Liu , Peiwen Feng , Jiao Tian , Baihua Chen , Shirui Dai , Liwei Zhang

Purpose

This study aimed to identify proteomic differences in the corneal epithelium of Neurotrophic Keratopathy (NK) patients with or without HSV-1 infection compared to normal donors.

Methods

Samples were divided into HSV-1-infected and non-infected NK groups, plus a control group. Corneal epithelial specimens were obtained via curettage/debridement, treated with TMT reagent, and analyzed by HPLC-MS/MS. Differentially expressed proteins underwent GO, KEGG, GSEA, and protein-protein interaction network analyses, with Western blotting validation.

Results

Compared to controls, non-HSV-1 NK patients showed 1228 differentially expressed proteins (771 downregulated, 457 upregulated), while HSV-1-infected NK patients had 939 (617 downregulated, 322 upregulated). Differential proteins play significant roles in many biological processes and pathways, such as epithelial-mesenchymal transition and interferon gamma response. Compared with the control group, there were 569 common differentially expressed proteins in HSV-1 infection and non-infection. We selected the top three upregulated proteins and the downregulated proteins. Their Western blotting results were consistent with the proteomics results.

Conclusion

This study has laid the foundation for the research on the mechanism of NK. It has been discovered that the upregulated (S100A2, TGM1, RPS28) and downregulated (ADH1C, EZH1, CHP2) proteins, which are significantly downregulated in the corneal epithelium of NK patients, may be used as diagnostic markers or therapeutic targets for NK in clinical practice.

目的：本研究旨在确定与正常供体相比，有无HSV-1感染的神经营养性角膜病变（NK）患者角膜上皮蛋白组学差异。方法：将标本分为hsv -1感染NK组和未感染NK组，另加对照组。角膜上皮标本刮除/清创，TMT试剂处理，HPLC-MS/MS分析。差异表达蛋白进行GO、KEGG、GSEA和蛋白相互作用网络分析，并进行Western blot验证。结果：与对照组相比，非hsv -1 NK患者有1228个差异表达蛋白（771个下调，457个上调），而感染hsv -1 NK患者有939个差异表达蛋白（617个下调，322个上调）。差异蛋白在许多生物过程和途径中发挥重要作用，如上皮-间质转化和干扰素γ反应。与对照组比较，1型单纯疱疹病毒感染和未感染组共有差异表达蛋白569个。我们选择了前三个上调蛋白和下调蛋白。他们的Western blotting结果与蛋白质组学结果一致。结论：本研究为NK的机制研究奠定了基础。研究发现，NK患者角膜上皮中显著下调的上调蛋白（S100A2、TGM1、RPS28）和下调蛋白（ADH1C、EZH1、CHP2）可作为NK的诊断标志物或临床治疗靶点。

{"title":"Proteomic analysis of corneal epithelial cells in patients with neurotrophic keratopathy","authors":"Jiarong Luo , Wentao Han , Shaohua Liu , Peiwen Feng , Jiao Tian , Baihua Chen , Shirui Dai , Liwei Zhang","doi":"10.1016/j.exer.2026.110899","DOIUrl":"10.1016/j.exer.2026.110899","url":null,"abstract":"<div><h3>Purpose</h3><div>This study aimed to identify proteomic differences in the corneal epithelium of Neurotrophic Keratopathy (NK) patients with or without HSV-1 infection compared to normal donors.</div></div><div><h3>Methods</h3><div>Samples were divided into HSV-1-infected and non-infected NK groups, plus a control group. Corneal epithelial specimens were obtained via curettage/debridement, treated with TMT reagent, and analyzed by HPLC-MS/MS. Differentially expressed proteins underwent GO, KEGG, GSEA, and protein-protein interaction network analyses, with Western blotting validation.</div></div><div><h3>Results</h3><div>Compared to controls, non-HSV-1 NK patients showed 1228 differentially expressed proteins (771 downregulated, 457 upregulated), while HSV-1-infected NK patients had 939 (617 downregulated, 322 upregulated). Differential proteins play significant roles in many biological processes and pathways, such as epithelial-mesenchymal transition and interferon gamma response. Compared with the control group, there were 569 common differentially expressed proteins in HSV-1 infection and non-infection. We selected the top three upregulated proteins and the downregulated proteins. Their Western blotting results were consistent with the proteomics results.</div></div><div><h3>Conclusion</h3><div>This study has laid the foundation for the research on the mechanism of NK. It has been discovered that the upregulated (S100A2, TGM1, RPS28) and downregulated (ADH1C, EZH1, CHP2) proteins, which are significantly downregulated in the corneal epithelium of NK patients, may be used as diagnostic markers or therapeutic targets for NK in clinical practice.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"265 ","pages":"Article 110899"},"PeriodicalIF":2.7,"publicationDate":"2026-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146104193","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}

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