Experimental eye research最新文献_第5页

Circadian rhythm disruption induces myopia in mice 昼夜节律紊乱诱导小鼠近视。

IF 2.7 2区医学 Q1 OPHTHALMOLOGY

Experimental eye research

Pub Date : 2025-12-22 DOI: 10.1016/j.exer.2025.110823

Wei-Ling Bai , Mei-Jun Wang , Jia-He Gan , Ying Huang , Zi-Han Liu , Cong-Ying Li , Ning-Li Wang , Shi-Ming Li

Emerging evidence suggests a link between circadian rhythm and myopia, with studies showing that retinal-specific knockout of the clock gene Bmal1 induces myopia in mice. This study aims to elucidate the relationship between circadian rhythm disruption (CRD) and myopia, and to investigate the potential mechanisms underlying CRD-mediated myopia development. Three-week-old C57BL/6J mice were entrained to a 12 h light/12 h dark (12L/12D) photoperiod for one week. Mice were then randomly assigned to the 12L/12D control group and the CRD groups. CRD groups were divided into two subgroups: Chronic jet lag (light cycle conditions with an 8 h dark advance every 2–3 days, CJL) and Irregular (light cycle conditions alternating among 16L/8D, 8L/16D and 12L/12D). Refraction and axial length (AL) were measured. Further analysis of pathogenic mechanisms was conducted using RNA sequencing. CRD shifted refraction (control vs Irregular: two weeks: 2.61 ± 0.91 D vs −3.97 ± 1.91 D, P = 0.01; four weeks: 1.64 ± 0.72 D vs −5.3 ± 1.09 D, P < 0.0001; control vs CJL: two weeks: 2.61 ± 0.91 D vs −3.93 ± 1.6 D, P = 0.004; four weeks: 1.64 ± 0.72 D vs −6.2 ± 1.36 D, P < 0.001) and increased AL (four weeks: control vs Irregular, 3.318 ± 0.01 mm vs 3.363 ± 0.008 mm, P = 0.001; control vs CJL, 3.318 ± 0.01 mm vs 3.359 ± 0.008 mm, P = 0.004) towards myopia. RNA-sequencing revealed significant enrichment of genes involved in neurotransmitter signaling pathways, including GABAergic synapses, glutamatergic synapses, dopaminergic synapses and synaptic vesicle cycles. This study indicates that circadian rhythm disruption can induce myopia in mice, with RNA-sequencing supporting the potential role of neurotransmitter signaling pathways.

新出现的证据表明，昼夜节律和近视之间存在联系，研究表明，敲除视网膜特异性时钟基因Bmal1会导致小鼠近视。本研究旨在阐明昼夜节律紊乱（circadian rhythm disruption， CRD）与近视的关系，并探讨CRD介导的近视发展的潜在机制。将3周龄C57BL/6J小鼠置于12小时光照/12小时黑暗（12L/12D）光周期1周。然后将小鼠随机分为12L/12D对照组和CRD组。CRD组分为两个亚组：慢性时差（每2-3天提前8小时黑暗的光周期条件，CJL）和不规则（光周期条件在16L/8D， 8L/16D和12L/12D之间交替）。测量折光和轴向长度（AL）。利用RNA测序进一步分析致病机制。CRD转变折射(控制vs不规则:两周:2.61±0.91 vs -3.97±1.91 D, P = 0.01; 4周:1.64±0.72 vs -5.3±1.09 D, P < 0.0001;控制vs CJL:两周:2.61±0.91 vs -3.93±1.6 D, P = 0.004; 4周:1.64±0.72 vs -6.2±1.36 D, P < 0.001),增加了艾尔(4周:控制和不规则,3.318±0.01毫米和3.363±0.008毫米,P = 0.001;控制vs CJL, 3.318±0.01毫米和3.359±0.008毫米,P = 0.004)对近视。rna测序结果显示，参与gaba能突触、谷氨酸能突触、多巴胺能突触和突触囊泡周期等神经递质信号通路的基因显著富集。这项研究表明，昼夜节律中断可以诱导小鼠近视，rna测序支持神经递质信号通路的潜在作用。

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引用次数: 0

Effect of increasing chain length on inhibition of evaporation by perfluoro compounds in an in vitro gravimetric assay 体外重量测定中增加链长对全氟化合物抑制蒸发的影响（无字数限制）。

IF 2.7 2区医学 Q1 OPHTHALMOLOGY

Experimental eye research

Pub Date : 2025-12-22 DOI: 10.1016/j.exer.2025.110824

Megan E. Cavet , Jason L. Vittitow , Douglas Borchman

Objective

Semifluorinated alkanes (SFAs) are amphiphilic molecules with a fluorinated carbon segment (F) and a hydrocarbon segment (H). Perfluorohexyloctane ophthalmic solution (F6H8; MIEBO®) is an anti-evaporative agent for dry eye that forms a long-lasting layer on the surface of the tear film. This in vitro study evaluated the impact of SFA chain length on intermolecular interactions, evaporation rate (R_evap), and inhibition of R_evap of saline to compare the anti-evaporative properties of various SFAs.

Methods

The SFAs F4H2, F4H5/CsA (cyclosporine ophthalmic solution 0.1 %; Vevye®), F6H7, F6H8, and F6H10 were evaluated. The R_evap of 1 mL of each SFA and saline alone or saline with 11 or 100 μL of the SFA layered over top were evaluated gravimetrically at 35 °C. Total sample weight was recorded every 10 min over 100 min, and R_evap was obtained from the slope of the best-fit line obtained by least squares linear regression analysis. The relative order (fluidity) of the SFAs was evaluated using Fourier transform infrared spectroscopy.

Results

The mean (SEM) inherent R_evap (mg/min) was 102 (25), 6.0 (0.6), 0.58 (0.20), 0.15 (0.017), and 0.12 (0.09) for F4H2, F4H5/CsA, F6H7, F6H8, and F6H10, respectively (n = 3–9). The R_evap of saline with a 100 μL F6H7, F6H8, and F6H10 layer was inhibited by 40 %, 80 %, and 66 %, respectively (p < 0.001 vs saline), and unchanged by F4H2 and F4H5/CsA. Only F6H8 had a significant inhibitory effect on R_evap of saline when applying an 11 μL drop (p < 0.0001 vs saline; n = 10–25). The SFA-SFA intermolecular interactions were greater with longer H and F chain lengths.

Conclusions

SFA chain length and volatility correlated with inhibition of the R_evap of saline with the longest chain length SFAs F6H8 and F6H10 having the maximal effect. These data support the suitability of F6H8 as a treatment for evaporative dry eye disease.

目的：半氟化烷烃（sfa）是具有氟化碳段(F)和烃段(H)的两亲分子。全氟己辛烷眼液（F6H8; MIEBO®）是干眼症的抗蒸发剂，在泪膜表面形成持久的层。本体外研究评估了SFA链长对生理盐水分子间相互作用、蒸发速率（Revap）以及对Revap的抑制作用的影响，以比较不同SFA的抗蒸发性能。方法：对SFAs F4H2、F4H5/CsA（环孢素眼用液0.1%;Vevye®）、F6H7、F6H8、F6H10进行评价。分别用1 mL的SFA和生理盐水，或在生理盐水上复盖11或100 μL的SFA，在35℃下进行重测。在100 min内每隔10 min记录一次总样品重量，通过最小二乘线性回归分析得到最佳拟合线的斜率得到Revap。利用傅里叶变换红外光谱法对sfa的相对序度（流动性）进行了评价。结果：F4H2、F4H5/CsA、F6H7、F6H8、F6H10的平均固有Revap (mg/min) （SEM）分别为102（25）、6.0（0.6）、0.58（0.20）、0.15（0.017）、0.12 (0.09)（n=3 ~ 9）。100 μL F6H7、F6H8和F6H10层对生理盐水Revap的抑制作用分别为40%、80%和66%（滴注11 μL时）。结论：SFA链长和挥发性与生理盐水对Revap的抑制作用相关，其中链长最长的SFA F6H8和F6H10对Revap的抑制作用最大。这些数据支持F6H8作为蒸发性干眼病治疗的适用性。

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引用次数: 0

Enhancement of DJ-1/ERK1/2 signaling as a therapeutic strategy for diabetic keratopathy 增强DJ-1/ERK1/2信号作为糖尿病角膜病变的治疗策略

IF 2.7 2区医学 Q1 OPHTHALMOLOGY

Experimental eye research

Pub Date : 2025-12-22 DOI: 10.1016/j.exer.2025.110820

Haoyu Li , Xinyue Sun , Hanhan Peng , Shaohua Liu , Liwei Zhang , Baihua Chen

Background

Diabetic keratopathy (DK) is a prevalent yet often overlooked complication of diabetes, marked by delayed corneal epithelial repair and impaired nerve regeneration. Despite its clinical significance, effective pharmacological interventions are still lacking, largely due to the limited understanding of its underlying molecular mechanisms.

Methods

Type 1 diabetic mice were used to evaluate corneal wound closure, nerve density, and oxidative stress after modulation of DJ-1 expression by plasmid transfection. Human corneal epithelial cells (HCECs) cultured under high-glucose conditions were assessed for mitochondrial membrane potential (JC-1 staining), intracellular reactive oxygen species (DCFH-DA staining), and cell proliferation (Ki67 staining). DJ-1 expression was enhanced by agonists, while ERK1/2 signaling was selectively inhibited. Apoptosis was detected by TUNEL staining, protein levels were analyzed by Western blotting, and mitochondrial morphology was examined by MitoTracker staining.

Results

High glucose disrupted mitochondrial function, elevated ROS, and reduced HCEC viability. DJ-1 restoration enhanced p-ERK1/2 signaling, attenuated oxidative stress, and promoted epithelial repair and nerve regeneration in diabetic mice. In vitro, DJ-1 overexpression preserved mitochondrial integrity, upregulated antioxidant defenses, and facilitated proliferation and migration, whereas ERK1/2 inhibition abolished these protective effects. Mechanistically, DJ-1 directly interacted with ERK1/2 and promoted nuclear translocation of p-ERK1/2, thereby activating antioxidant pathways.

Conclusion

The DJ-1/ERK1/2 signaling axis plays a pivotal role in maintaining corneal epithelial and neural homeostasis in diabetes. DJ-1 targeting may represent a promising therapeutic strategy for DK.

糖尿病性角膜病变（DK）是一种常见但常被忽视的糖尿病并发症，其特征是角膜上皮修复延迟和神经再生受损。尽管具有临床意义，但有效的药物干预仍然缺乏，这主要是由于对其潜在分子机制的了解有限。方法采用质粒转染调节DJ-1表达后，观察1型糖尿病小鼠角膜创面闭合、神经密度和氧化应激的变化。对高糖条件下培养的人角膜上皮细胞（HCECs）进行线粒体膜电位（JC-1染色）、细胞内活性氧（DCFH-DA染色）和细胞增殖（Ki67染色）的检测。激动剂可增强DJ-1的表达，而ERK1/2信号被选择性抑制。TUNEL染色检测细胞凋亡，Western blotting检测蛋白水平，MitoTracker染色检测线粒体形态。结果高糖破坏线粒体功能，升高ROS，降低HCEC活力。DJ-1修复增强糖尿病小鼠p-ERK1/2信号，减轻氧化应激，促进上皮修复和神经再生。在体外，DJ-1过表达可保持线粒体完整性，上调抗氧化防御，促进增殖和迁移，而ERK1/2抑制可消除这些保护作用。在机制上，DJ-1直接与ERK1/2相互作用，促进p-ERK1/2核易位，从而激活抗氧化途径。结论DJ-1/ERK1/2信号轴在糖尿病角膜上皮和神经稳态的维持中起关键作用。DJ-1靶向治疗可能是一种很有前途的治疗DK的策略。

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引用次数: 0

Precise biometric measurement of the mouse eye using optical coherence tomography based on optic-nerve-head imaging 基于视神经头成像的光学相干断层扫描对小鼠眼睛进行精确的生物测量。

IF 2.7 2区医学 Q1 OPHTHALMOLOGY

Experimental eye research

Pub Date : 2025-12-22 DOI: 10.1016/j.exer.2025.110821

Sisi Chen , Peifeng Zhang , Haiyao Wang , Jieying Shen , Hao Chen , Qiufeng Lin , Shilei Wang , Jiadi Zhu , Qiongsi Wang , Furong Huang , Zi Jin , Yilei Shao , Yuanyuan Wang , Fan Lu , Meixiao Shen

Due to the availability of various mouse strains with well-defined genomes, mice have become pivotal models for ocular developmental research. Accurate and highly repeatable biometric measurements are crucial for investigating myopia in experimental animals. This study aimed to develop a precise methodology for comprehensive assessment of ocular biometrics in mice. We developed the custom-built spectral domain optical coherence tomography (SD-OCT) system with an axial resolution of 4.3 μm, and an imaging depth of 4.1 mm in tissue. Three-dimensional biometric parameters exhibited superior precision (standard deviation = 5–6 μm, intraclass correlation coefficients (ICC) ≥ 0.78) compared to each two-dimensional parameter (standard deviation = 6–10 μm, ICC ≥0.62). Excellent repeatability was observed in the measurement of anterior chamber depth, vitreous chamber depth, retinal thickness, and axial thickness in mouse eyes, with ICC≥ 0.79 for optic nerve head (ONH) localization results, surpassing the classical non-ONH method (ICC ≥0.62, except for retinal thickness where ICC is 0.33). Notably, ICC and within-subject standard deviation of AL were 0.978 and 5.14 μm, respectively, in ONH localization results, while these values were 0.873 and 11.69 μm, respectively, in classical non-ONH results. Based on the custom-built SD-OCT, this study proposes a precise in vivo ocular biometric measurement method for mouse using the combination of a radial 3D scan mode and novel ONH localization imaging, which provides a useful method for the study of ocular physiology and pathological growth.

由于具有明确基因组的各种小鼠品系的可用性，小鼠已成为眼发育研究的关键模型。准确和高度可重复的生物测量对于研究实验动物的近视至关重要。本研究旨在建立一种精确的方法来全面评估小鼠眼部生物特征。我们开发了定制的光谱域光学相干断层扫描（SD-OCT）系统，轴向分辨率为4.3 μm，组织成像深度为4.1 mm。三维生物特征参数的精度（标准差= 5 ~ 6 μm，类内相关系数(ICC)≥0.78）优于二维参数（标准差= 6 ~ 10 μm, ICC≥0.62）。在测量小鼠眼睛前房深度、玻璃体室深度、视网膜厚度和轴向厚度时，观察到极好的重复性，视神经头（ONH）定位结果的ICC≥0.79，超过经典的非ONH方法（ICC≥0.62，视网膜厚度除外，其中ICC为0.33）。值得注意的是，在ONH定位结果中，ICC和受试者内标准偏差分别为0.978和5.14 μm，而在经典的非ONH结果中，这两个值分别为0.873和11.69 μm。本研究基于定制的SD-OCT，提出了一种结合径向三维扫描模式和新型ONH定位成像的小鼠体内眼生物特征精确测量方法，为研究眼生理和病理生长提供了一种有用的方法。

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引用次数: 0

Recent advances of novel nanoformulations combatting blue light hazards in the retina 对抗视网膜蓝光危害的新型纳米制剂的最新进展

IF 2.7 2区医学 Q1 OPHTHALMOLOGY

Experimental eye research

Pub Date : 2025-12-19 DOI: 10.1016/j.exer.2025.110806

Somnath Ghosh , Pritam Parua , Koushik Jana , Shirsa Kumar Ghosh , Abhijit Ghosh , Biplab Debnath , Jitu Halder , Rakesh Kumar Sahoo , Vineet Kumar Rai , Priyanka Dash , Chandan Das , Biswakanth Kar , Goutam Ghosh , Goutam Rath

Exposure to blue light significantly threatens retinal health, affecting approximately 73 % of the global population. It impairs vision, lowers the quality of life, and adds to public health challenges. Its treatment is getting difficult due to chronicity, limited drug efficacy, side effects, and ocular barriers that hinder conventional drug delivery. Nanoformulations (NFs) have gained attention as adaptable drug delivery systems (DDSs), offering controlled release and customizable physicochemical characteristics. Their application in ocular therapy has shown promise for targeting both anterior and posterior segments of the eye. By accommodating a broad spectrum of therapeutic agents, these nanocarriers help address the limitations of traditional retinal drug delivery methods and offer potential in mitigating blue light-induced retinal damage. Several NFs have shown significant promise in addressing blue light hazards and the retina-related diseases through various mechanisms. Nano-based formulations offer promising strategies for protecting the retina and treating retinal diseases caused by blue light exposure. Antioxidant-loaded liposomes and hydrogels, such as those containing lutein and zeaxanthin, help reduce oxidative stress. In contrast, curcumin-loaded nanoparticles (Cur-NPs) mitigate inflammation in conditions like age-related macular degeneration (AMD) and diabetic retinopathy (DR). Polymeric NPs enable gene-specific silencing of pathogenic targets, and metallic NPs enhance photothermal therapy by selectively destroying abnormal retinal cells. These advanced delivery systems, including protective nanofilms, offer improved bioavailability, targeted delivery, and minimal side effects, making them effective tools in combating retinal damage. This review emphasizes the potential of NFs for advanced drug delivery against blue light-induced retinal hazards, highlighting pharmaceutical and pharmacological findings, recent insights, key challenges, and proposed solutions for a better future.

蓝光暴露严重威胁视网膜健康，影响全球约73%的人口。它损害视力，降低生活质量，并增加了公共卫生挑战。由于慢性、有限的药物疗效、副作用和阻碍常规药物传递的眼屏障，其治疗变得越来越困难。纳米制剂（NFs）作为适应性药物传递系统（dds）已经引起了人们的关注，它提供了可控的释放和可定制的物理化学特性。它们在眼部治疗中的应用已经显示出针对眼睛前段和后段的希望。通过适应广泛的治疗药物，这些纳米载体有助于解决传统视网膜药物递送方法的局限性，并提供减轻蓝光引起的视网膜损伤的潜力。一些NFs通过各种机制在解决蓝光危害和视网膜相关疾病方面显示出重大的希望。纳米配方为保护视网膜和治疗蓝光照射引起的视网膜疾病提供了有前途的策略。含有抗氧化剂的脂质体和水凝胶，如含有叶黄素和玉米黄质的脂质体和水凝胶，有助于减少氧化应激。相反，姜黄素纳米颗粒（curcumin- nps）可以减轻年龄相关性黄斑变性（AMD）和糖尿病性视网膜病变（DR）等疾病的炎症。聚合NPs使致病靶点的基因特异性沉默，金属NPs通过选择性破坏异常视网膜细胞来增强光热治疗。这些先进的给药系统，包括保护性纳米膜，提供了更好的生物利用度、靶向给药和最小的副作用，使其成为对抗视网膜损伤的有效工具。这篇综述强调了NFs在对抗蓝光诱导的视网膜危害的高级药物递送方面的潜力，重点介绍了药物和药理学的发现，最近的见解，关键挑战，以及为更好的未来提出的解决方案。

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引用次数: 0

Deletion of versican V0/V2 isoforms in mice leads to retinal dysplasia 小鼠中versican V0/V2异构体的缺失导致视网膜发育不良。

IF 2.7 2区医学 Q1 OPHTHALMOLOGY

Experimental eye research

Pub Date : 2025-12-19 DOI: 10.1016/j.exer.2025.110819

Anja K. Hoffmann , Nadine Bauer , Michelle C. Geigenfeind , Silke Seibold , Roswitha Seitz , Rudolf Fuchshofer , Ernst R. Tamm , Andrea E. Dillinger

Versican, a chondroitin sulfate proteoglycan, is a component of the interphotoreceptor matrix (IPM) and vitreous body in both mouse and human eyes. Mutations in VCAN, the gene encoding the versican core protein, cause Wagner vitreoretinopathy, a disorder characterized by vitreous syneresis, progressive chorioretinal atrophy, and early-onset retinal detachment. Versican exists in four isoforms (V0, V1, V2, V3), which differ in their glycosaminoglycan (GAG) attachment domains. To investigate isoform-specific functions of versican in retinal development and homeostasis, we examined VCAN^tm1Zim mice, which lack the V0 and V2 isoforms. Retinal development was assessed at postnatal days 1, 5, and 15, and at 4 and 8 weeks of age using light and transmission electron microscopy, morphometric analyses, and immunohistochemistry for RPE65, laminin, and collagen IV. Hyaluronan distribution was assessed using biotinylated versican G1 hyaluronan-binding protein, and in situ hybridization localized isoform-specific mRNA expression. Loss of V0 and V2 resulted in early-onset retinal infoldings, visible by P1, with fold cores containing cellular debris and retinal pigmented epithelium (RPE)-derived melanosomes. However, the RPE monolayer remained structurally intact, and no differences in RPE cell number or size were detected between wild-type and mutant animals. In wild-type mice, V0 and V2 transcripts were present throughout all retinal layers and the RPE. No morphological abnormalities were observed in Bruch's membrane or the vitreoretinal border based on staining for collagen IV, laminin, or hyaluronan. These findings suggest that V0/V2 isoforms play a critical role in maintaining adhesion between the neural retina and the RPE, likely through regulation of the IPM microenvironment. Based on these results, it is plausible that photoreceptor degeneration and dysfunction in Wagner vitreoretinopathy arises from isoform-specific disturbances in the IPM secondary to versican deficiency or dysfunction.

Versican是一种硫酸软骨素蛋白多糖，是小鼠和人眼感光基质（IPM）和玻璃体的成分。编码versican核心蛋白的基因VCAN突变导致Wagner玻璃体视网膜病变，这是一种以玻璃体联合、进行性绒毛膜视网膜萎缩和早发性视网膜脱离为特征的疾病。Versican存在于四种异构体（V0, V1, V2, V3）中，它们的糖胺聚糖（GAG）附着域不同。为了研究versican在视网膜发育和体内平衡中的亚型特异性功能，我们研究了缺乏V0和V2亚型的VCANtm1Zim小鼠。在出生后第1、5、15天和第4、8周龄时，使用光镜、透射电镜、形态计量学分析和免疫组织化学检测RPE65、层粘胶蛋白和IV型胶原，评估视网膜发育情况。使用生物素化的versicg1透明质酸结合蛋白评估透明质酸分布，并进行原位杂交定位同种异构体特异性mRNA表达。V0和V2的缺失导致早发性视网膜褶皱，如图1所示，褶皱核心含有细胞碎片和视网膜色素上皮（RPE）衍生的黑素体。然而，RPE单层在结构上保持完整，并且在野生型和突变型动物之间没有检测到RPE细胞数量或大小的差异。在野生型小鼠中，V0和V2转录本存在于所有视网膜层和RPE中。基于IV型胶原蛋白、层粘连蛋白或透明质酸染色，Bruch膜或玻璃体视网膜边界未见形态学异常。这些发现表明，V0/V2亚型可能通过调控IPM微环境，在维持神经视网膜和RPE之间的粘附方面发挥关键作用。基于这些结果，瓦格纳玻璃体视网膜病变的光感受器变性和功能障碍似乎是由继发于versican缺乏或功能障碍的IPM的同型特异性紊乱引起的。

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引用次数: 0

Caspofungin-loaded dissolving microneedles for transcorneal delivery in fungal keratitis 载caspofunin溶解微针用于真菌性角膜炎经角膜给药

IF 2.7 2区医学 Q1 OPHTHALMOLOGY

Experimental eye research

Pub Date : 2025-12-19 DOI: 10.1016/j.exer.2025.110812

Behnam Aghaei , Mahboobeh Jafari , Samira Sadat Abolmaali , Kamiar Zomorodian , Ali Mohammad Tamaddon

Fungal keratitis is a severe corneal infection that can lead to vision loss and requires prompt, effective antifungal treatment with optimal corneal penetration and minimal toxicity. Conventional treatments, such as natamycin and voriconazole eye drops, face challenges like poor bioavailability, fungal resistance, and epithelial toxicity. In this study, we developed and evaluated dissolvable microneedle (MN) arrays loaded with caspofungin, an inhibitor of β-(1, 3)-D-glucan synthase with a lower resistance compared to azole-based treatments. MNs composed of hyaluronic acid (HA) and polyvinylpyrrolidone (PVP) were fabricated using a micromolding technique. HA provides bioadhesion and hydration, while PVP enhances mechanical strength and solubility. The HA-PVP matrix was designed to ensure the mechanical integrity required for corneal penetration, while allowing rapid dissolution after application. To assess drug delivery, fluorescein isothiocyanate (FITC)-labeled caspofungin was incorporated into the MNs, which facilitated local delivery and distribution throughout the corneal stroma with minimal lateral diffusion. Ex vivo studies using a bovine corneal model demonstrated a five-fold increase in drug delivery compared to conventional eye drops. Antifungal activity of the caspofungin in the MNs was confirmed against Candida albicans, Candida parapsilosis, Candida glabrata, and Aspergillus fumigatus using agar diffusion assays and comparing the zones of inhibition with standard caspofungin solutions. These findings suggest that caspofungin-loaded dissolving MNs represent a promising, minimally invasive approach for overcoming the challenges of ocular drug delivery in fungal keratitis.

真菌性角膜炎是一种严重的角膜感染，可导致视力丧失，需要及时有效的抗真菌治疗，最佳的角膜穿透和最小的毒性。传统的治疗方法，如纳他霉素和伏立康唑滴眼液，面临着生物利用度差、真菌耐药性和上皮毒性等挑战。在这项研究中，我们开发并评估了装载caspofungin的可溶微针（MN）阵列，caspofungin是一种β-(1,3)- d -葡聚糖合成酶抑制剂，与基于唑的处理相比具有更低的耐药性。采用微模塑技术制备了透明质酸（HA）和聚乙烯吡咯烷酮（PVP）组成的纳米粒子。透明质酸提供生物黏附和水合作用，而PVP提高机械强度和溶解度。HA-PVP基质旨在确保角膜穿透所需的机械完整性，同时允许应用后快速溶解。为了评估药物传递，将异硫氰酸荧光素（FITC）标记的caspofungin加入到MNs中，这有助于局部传递和分布在整个角膜基质中，并具有最小的外侧扩散。使用牛角膜模型的离体研究表明，与传统滴眼液相比，药物输送增加了五倍。通过琼脂扩散试验，并与标准溶液进行抑制区比较，证实了MNs中caspofunins对白色念珠菌、假丝酵母菌、光假丝酵母菌和烟曲霉的抑菌活性。这些发现表明，载caspofunin的溶解性MNs代表了一种有希望的、微创的方法，可以克服真菌性角膜炎眼部给药的挑战。

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引用次数: 0

The homeobox gene, dmbx1a, is required for the development and maintenance of bipolar and photoreceptor cells in the zebrafish retina 同源盒基因dmbx1a是斑马鱼视网膜中双极和光感受器细胞发育和维持所必需的

IF 2.7 2区医学 Q1 OPHTHALMOLOGY

Experimental eye research

Pub Date : 2025-12-19 DOI: 10.1016/j.exer.2025.110809

Amanda Miles, Jeffrey Stulberg, Vincent Tropepe

Retinal neurogenesis at early postembryonic stages is conserved among vertebrates for its role in homeostatic tissue growth and its dysfunction in humans may partially account for diseases of retinal growth or other retinal dystrophies. However, the molecular mechanisms underlying neurogenic growth of the postembryonic retina are poorly characterized. We report a novel role for the homeobox gene dmbx1a in tissue growth, survival of differentiated cells, bipolar differentiation, and photoreceptor maintenance in the postembryonic zebrafish retina. Specifically, dmbx1a mutants exhibited reduced eye size over time, increased cell death in differentiated cells derived from progenitor cells of the central retina and ciliary marginal zone, and age- and light-dependent photoreceptor dysmorphism. By examining the early changes in the retinal transcriptome of dmbx1a mutants, we were able to determine changes in gene expression that are associated with the observed retinal defects. Among this transcriptomic data, there is evidence to suggest that dmbx1 affects known retinal-associated genes implicated in retinal degenerative conditions and ocular impairments, with a particular emphasis on ciliogenesis factors important for outer segment growth in photoreceptors.

胚胎后早期的视网膜神经发生在脊椎动物中是保守的，因为它在体内平衡组织生长中起作用，它在人类中的功能障碍可能部分解释了视网膜生长疾病或其他视网膜营养不良。然而，胚胎后视网膜神经源性生长的分子机制尚不清楚。我们报道了在胚胎后斑马鱼视网膜中，同源盒基因dmbx1a在组织生长、分化细胞存活、双极分化和光感受器维持中的新作用。具体而言，随着时间的推移，dmbx1a突变体表现出眼睛尺寸减小，来自中央视网膜和睫状体边缘区祖细胞的分化细胞死亡增加，以及年龄和光依赖性光感受器畸形。通过检查dmbx1a突变体视网膜转录组的早期变化，我们能够确定与观察到的视网膜缺陷相关的基因表达变化。在这些转录组学数据中，有证据表明dmbx1影响已知的视网膜相关基因，这些基因与视网膜退行性疾病和眼部损伤有关，特别强调对光感受器外段生长重要的纤毛发生因子。

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引用次数: 0

Noncoding RNAs regulating the insulin signaling pathway: a new therapeutic approach in diabetic retinopathy 调节胰岛素信号通路的非编码rna：治疗糖尿病视网膜病变的新途径

IF 2.7 2区医学 Q1 OPHTHALMOLOGY

Experimental eye research

Pub Date : 2025-12-18 DOI: 10.1016/j.exer.2025.110814

Jiayue Wang , Tongyan Liu , Jinrong Lu , Xinlei Yang , Xiaoling Feng , Yuan Li

Diabetic retinopathy (DR), one of the microvascular diseases of diabetes mellitus, remains one of the leading causes of blindness worldwide. Preclinical and limited human tissue studies indicate that dysregulation of insulin signaling is central to the pathophysiology of DR, at least at the retinal vascular level. Multiple independent preclinical studies have implicated noncoding RNAs (ncRNAs, including microRNAs (miRNAs), long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs)) as potent modulators of insulin signaling within retinal cells. The modulatory ncRNAs act by targeting essential components of the insulin cascade, like Insulin Receptor Substrate 1 (IRS1), Phosphoinositide 3-Kinase/Akt (Protein Kinase B) pathway (PI3K/Akt), Glucose Transporter Type 4 (GLUT4), Phosphatase and Tensin Homolog (PTEN), and Insulin-Like Growth Factor-1 Receptor (IGF-1R), to modulate glucose metabolism, oxidative stress response, angiogenesis, and apoptosis under hyperglycemic conditions. This review collates current data on the polyvalent functionality of ncRNAs in modulating insulin signaling and potentially acting as biomarkers and therapeutic targets for DR. The review also delves into how specific ncRNAs can directly and indirectly reduce disease progression by targeting the insulin cascade, versus those that can repress such progression. Since the treatment of DR has a limited scope and efficacy, targeting this ncRNA-insulin signaling axis may offer an intriguing new opportunity to discover novel therapeutics.

糖尿病视网膜病变（DR）是糖尿病的一种微血管疾病，是世界范围内致盲的主要原因之一。临床前和有限的人体组织研究表明，胰岛素信号的失调是DR病理生理的核心，至少在视网膜血管水平上是这样。多项独立的临床前研究表明，非编码rna （ncRNAs，包括microRNAs （miRNAs）、长链非编码rna （lncRNAs）和环状rna (circRNAs)）是视网膜细胞内胰岛素信号的有效调节剂。调节ncRNAs通过靶向胰岛素级联的基本成分，如胰岛素受体底物1 （IRS1）、磷酸肌醇3-激酶/Akt（蛋白激酶B）通路（PI3K/Akt）、葡萄糖转运蛋白4型（GLUT4）、磷酸酶和紧张素同源物（PTEN）和胰岛素样生长因子-1受体（IGF-1R），在高血糖条件下调节葡萄糖代谢、氧化应激反应、血管生成和细胞凋亡。这篇综述整理了目前关于ncrna在调节胰岛素信号传导和潜在作为dr的生物标志物和治疗靶点方面的多价功能的数据。这篇综述还深入探讨了特异性ncrna如何通过靶向胰岛素级联直接或间接地减少疾病进展，而不是那些可以抑制这种进展的ncrna。由于DR的治疗范围和疗效有限，靶向ncrna -胰岛素信号轴可能为发现新的治疗方法提供了一个有趣的新机会。

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Myopia pathogenesis and vasoactive intestinal peptide: Molecular mechanisms, experimental models, and clinical implications 近视发病与血管活性肠肽：分子机制、实验模型及临床意义

IF 2.7 2区医学 Q1 OPHTHALMOLOGY

Experimental eye research

Pub Date : 2025-12-18 DOI: 10.1016/j.exer.2025.110810

Camila Grubsic , Ricardo Céspedes , Felipe Tapia , Oliver Schmachtenberg

Myopia is the most common refractive error worldwide and is projected to affect half of the global population by 2050, with high myopia significantly increasing the risk of vision-threatening complications. While multiple genetic, environmental and lifestyle factors contribute to myopia onset and progression, recent findings suggest a role for vasoactive intestinal peptide (VIP) and its receptor VIPR2 in ocular growth regulation. This review summarizes current knowledge about myopia pathogenesis and the diverse factors involved, focusing on the molecular, genetic, pharmacological, and clinical findings regarding VIP/VIPR2 signaling in the eye. Evidence from animal models reveals a complex interaction between VIP and myopia, with VIP agonists/antagonists either protecting from or promoting myopia depending on model and dosage, VIPR2 knockout mice developing spontaneous myopia, and VIP interacting with circadian rhythms and atropine signaling. Genetic association studies have identified both risk and protective VIPR2 haplotypes, with environmental light exposure modulating their effects. Mechanistic studies suggest that VIP regulates choroidal and scleral remodeling, acting in concert with dopaminergic, cholinergic, and retinoic acid pathways. We propose that VIP/VIPR2 is a key modulator of emmetropization and a promising therapeutic target for myopia, though species-specific effects and context-dependency remain to be resolved.

近视是世界上最常见的屈光不正，预计到2050年将影响全球一半的人口，高度近视显著增加了视力威胁并发症的风险。虽然多种遗传、环境和生活方式因素会导致近视的发生和发展，但最近的研究结果表明，血管活性肠肽（VIP）及其受体VIPR2在眼部生长调节中起着重要作用。本文综述了目前关于近视发病机制及其相关因素的研究进展，重点介绍了VIP/VIPR2信号在眼睛中的分子、遗传、药理学和临床研究结果。来自动物模型的证据表明，VIP与近视之间存在复杂的相互作用，VIP激动剂/拮抗剂根据模型和剂量的不同可以预防或促进近视，VIPR2敲除小鼠发生自发性近视，VIP与昼夜节律和阿托品信号相互作用。遗传关联研究已经确定了风险和保护性VIPR2单倍型，环境光暴露调节了它们的作用。机制研究表明，VIP调节脉络膜和巩膜重塑，与多巴胺能、胆碱能和视黄酸途径协同作用。我们认为VIP/VIPR2是近视的关键调节因子和有希望的治疗靶点，尽管物种特异性效应和环境依赖性仍有待解决。

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引用次数: 0