Experimental eye research最新文献_第10页

A machine learning-based model for the prediction of thyroid eye disease with oxidative stress-related biomarkers 基于机器学习的氧化应激相关生物标志物甲状腺眼病预测模型

IF 2.7 2区医学 Q1 OPHTHALMOLOGY

Experimental eye research

Pub Date : 2026-03-01 Epub Date: 2025-12-29 DOI: 10.1016/j.exer.2025.110835

Jin Liu , Weijin Qian , Li Yang , Tianyi Zhu , Yining Wei , Lianfei Fang , Sijie Fang , Jing Sun , Huifang Zhou

Thyroid eye disease (TED), the most common adult orbital disease, can significantly impair patients' quality of life. Currently, effective diagnostic and predictive models for TED remain limited, making early intervention and personalized treatment for patients challenging. Oxidative stress (OS) plays an important role in pathogenesis of TED, and OS related biomarkers may serve as good candidates for TED prediction. Here, we integrated the peripheral blood bulk-RNA sequencing data and clinical features of 152 TED, 61 health control (HC), and 20 patients with simple Graves’ disease (GD) to identify potential biomarkers. The intersection of TED-HC and TED-GD differentially expressed genes (DEGs) identified 1220 genes strongly correlated with TED. Enrichment analysis showed upregulation of OS-related biological processes in patients with TED. Integration of DEGs, WGCNA results, and OS-related genes identified six genes as candidate biomarkers. Machine learning algorithms suggested three critical candidate genes (KLF2, SELENON, TXNRD1) with high predictive value and were used to construct an oxidative stress-related predictive gene score (OSRPGS). Receiver operating characteristic curve confirmed the predictive value of OSRPGS with an AUC value of 0.733 (TED vs HC) and 0.705 (TED vs GD). Further patient stratification analysis confirmed that the OSRPGS was associated with tear secretion dysfunction. Furthermore, immune infiltration analysis suggested an upregulation of innate immune responses, especially the monocytes/macrophages subtypes, indicating the initiation of OS-related inflammation. Collectively, our study provides a reliable tool for TED prediction and risk assessment based on OS-related biomarkers. OSRPGS may help with the early recognition and intervention in patients with TED.

甲状腺眼病（TED）是成人最常见的眼窝疾病，严重影响患者的生活质量。目前，有效的TED诊断和预测模型仍然有限，这使得患者的早期干预和个性化治疗具有挑战性。氧化应激（Oxidative stress， OS）在TED的发病机制中起重要作用，而氧化应激相关的生物标志物可能是预测TED的良好候选物。在这里，我们整合了152名TED， 61名健康对照（HC）和20名单纯性格雷夫斯病（GD）患者的外周血大体积rna测序数据和临床特征，以确定潜在的生物标志物。TED- hc和TED- gd差异表达基因（DEGs）的交集鉴定出1220个与TED密切相关的基因。富集分析显示，TED患者的os相关生物学过程上调。整合deg、WGCNA结果和os相关基因，鉴定出6个基因作为候选生物标志物。机器学习算法提出了三个具有高预测价值的关键候选基因（KLF2， SELENON, TXNRD1），并用于构建氧化应激相关预测基因评分（OSRPGS）。受试者工作特征曲线证实了OSRPGS的预测价值，其AUC值分别为0.733 （TED vs HC）和0.705 （TED vs GD）。进一步的患者分层分析证实OSRPGS与泪液分泌功能障碍有关。此外，免疫浸润分析表明先天免疫反应上调，特别是单核/巨噬细胞亚型，表明os相关炎症的开始。总之，我们的研究为基于os相关生物标志物的TED预测和风险评估提供了可靠的工具。OSRPGS可能有助于对TED患者的早期识别和干预。

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引用次数: 0

Non-neuronal cell microenvironment control retinal vascular remodeling by CST3 in the oxygen-induced retinopathy in mice 非神经元细胞微环境通过CST3调控氧致视网膜病变小鼠视网膜血管重构。

IF 2.7 2区医学 Q1 OPHTHALMOLOGY

Experimental eye research

Pub Date : 2026-03-01 Epub Date: 2026-01-12 DOI: 10.1016/j.exer.2026.110860

Ming-yan Du , Chao Qu , Tu-jing Zhao , Yan-hui Deng , Lin Ye , Hua-ping Tian , Run-ze Li , Zheng Li , Hao-jue Xu , Jie Li , Liang Zhou , Yi Shi , Lu-lin Huang

Retinopathy of prematurity (ROP) remains the leading cause of blindness in premature infants owing to abnormal retinal blood vessels development,but molecular mechanisms are still not fully elucidated. Oxygen-induced retinopathy (OIR) mouse is the extensively used angiogenesis model for the study of ROP pathogenesis. In this study, we investigated five cell types that composed the microenvironment of retinal vessels in OIR mice by single-cell RNA sequencing (scRNA-seq) and revealed a complex and time-dependent regulation of vascular arrest and angiogenesis in the OIR microenvironment. Importantly, we also observe that Müller glia exhibit robust expression of CST3 (cysteine protease inhibitor cystatin C) during the early phase of hypoxic adaptation, leading to capillary morphogenesis in the hyaloid, disrupting physiological vascular patterning and contributing to OIR development. Altogether, our study reveals pivotal roles of the retinal microenvironment in both normal vascularization and ROP progression, suggesting that CST3 is a potential therapeutic target for ROP.

早产儿视网膜病变（ROP）是导致早产儿失明的主要原因，主要是由于视网膜血管发育异常，但其分子机制尚未完全阐明。氧诱导视网膜病变（OIR）小鼠是目前广泛应用于ROP发病机制研究的血管生成模型。在这项研究中，我们通过单细胞RNA测序（scRNA-seq）研究了构成OIR小鼠视网膜血管微环境的五种细胞类型，揭示了OIR微环境中血管骤停和血管生成的复杂和时间依赖性调控。重要的是，我们还观察到，在低氧适应的早期阶段，m ller胶质细胞表现出CST3（半胱氨酸蛋白酶抑制剂胱抑素C）的强烈表达，导致玻璃体中的毛细血管形态发生，破坏生理血管模式并促进OIR的发展。总之，我们的研究揭示了视网膜微环境在正常血管化和ROP进展中的关键作用，表明CST3是ROP的潜在治疗靶点。

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引用次数: 0

Rapid anterior segment and divergent corneal shape remodeling drive astigmatic compensation in the chick model 快速前段和发散性角膜形状重塑驱动鸡模型的散光代偿

IF 2.7 2区医学 Q1 OPHTHALMOLOGY

Experimental eye research

Pub Date : 2026-03-01 Epub Date: 2026-01-13 DOI: 10.1016/j.exer.2026.110861

Yuanyuan Liang , Tsz Wing Leung , Patience Ansomah Ayerakwah , Byung Soo Kang , Chea-su Kee

This study investigated early temporal dynamics of ocular compensation to imposed astigmatic blur, specifically anterior segment alterations in a chick model. Fifty-four chickens were equally randomized to treatment or control groups at post-hatching day 5 (baseline, T0). Crossed-cylindrical lens (+4.00 DS/−8.00 DC) was used to induce astigmatic blur on the right eye for two weeks: With-the-rule (WTR, axis 90°) and Against-the-rule (ATR, axis 180°) astigmatism. Ocular axial dimensions and objective refraction were measured daily for the first four days (T0-T3), and at one (T7) and two weeks (T14). Corneal topography was measured at T3, T7 and T14. Our results showed that chicks treated with crossed-cylindrical lenses developed significantly higher refractive astigmatism compared to the control group (all p < 0.01), plateauing within two days. Corneal astigmatism diverged over two weeks, increasing in the WTR group but decreasing in the ATR groups, while internal astigmatism showed opposite trends. Critically, anterior segment changes emerged by T3: the ATR group exhibited a significantly deeper anterior chamber (T3: p = 0.034), and both treatment groups showed significantly thinner crystalline lenses (ATR: T2, p = 0.008; T3, p = 0.007; WTR: T3, p = 0.043) compared to controls. These changes persisted throughout the treatment. To conclude, refractive astigmatism compensated rapidly (plateauing within two days) in response to astigmatic blur, while corneal astigmatism exhibited divergent changes over two weeks. The persistent anterior segment alterations—lens thinning and anterior chamber deepening—demonstrate a key compensatory role for anterior ocular structures beyond corneal plasticity alone.

本研究调查了早期的时间动态眼代偿强加的散光模糊，特别是前段的变化，在一个小鸡模型。54只鸡在孵化后第5天（基线，T0）随机分为处理组和对照组。采用交叉柱状晶状体（+4.00 DS/−8.00 DC）诱导右眼散光模糊2周：顺行（WTR，轴90°）和反行（ATR，轴180°）散光。前4天（T0-T3）、第1周（T7）和第2周（T14）每天测量眼轴尺寸和物镜屈光度。在T3、T7、T14时测量角膜地形图。结果表明，与对照组相比，经交叉柱面透镜处理的雏鸡的屈光散光明显增加（p < 0.01），并在2天内趋于稳定。角膜散光在两周内出现分化，WTR组增加，ATR组减少，而内部散光则呈现相反的趋势。重要的是，T3出现了前段的改变：与对照组相比，ATR组的前房明显加深（T3: p = 0.034），两个治疗组的晶状体明显变薄（ATR: T2, p = 0.008; T3, p = 0.007; WTR: T3, p = 0.043）。这些变化在整个治疗过程中持续存在。综上所述，屈光散光对散光模糊的反应补偿迅速（2天内稳定），而角膜散光在两周内表现出不同的变化。持续的前段改变——晶状体变薄和前房加深——表明除了角膜可塑性外，前眼结构还具有重要的代偿作用。

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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 : 2026-03-01 Epub 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

Development of a microscopy-based diagnostic test for alkali injury-induced limbal stem cell deficiency through Autofluorescence Multispectral Imaging 基于自体荧光多光谱成像的碱损伤诱导的角膜缘干细胞缺乏症显微诊断方法的建立。

IF 2.7 2区医学 Q1 OPHTHALMOLOGY

Experimental eye research

Pub Date : 2026-03-01 Epub Date: 2025-12-23 DOI: 10.1016/j.exer.2025.110829

Xiaohu Xu , Lina Sprogyte , Alexander Richardson , Lamia Nureen , Ewa Magdalena Goldys , Nick Di Girolamo , Abbas Habibalahi

Diagnosing limbal stem cell deficiency (LSCD) remains challenging, and this study evaluates a newly developed Autofluorescence Multispectral Imaging (AFMI) technology for its diagnostic potential. Unstained fixed corneal cross-sections from 36 mice were used in this study. The right eyes of these mice had alkali-induced LSCD, while the left eyes served as healthy controls. Autofluorescence multispectral images of the corneal epithelium were acquired across multiple spectral channels to track changes in endogenous fluorophore spectra. Big data analytics and machine learning classifiers were applied to differentiate LSCD-affected from healthy tissues. The performance of this technique was evaluated by histological evaluation. Imaging was conducted on both the Operetta CLS (PerkinElmer) for research applications and a custom-modified Olympus IX83 system designed for potential clinical translation. Significant differences in autofluorescence signal intensities (p < 0.0001) were observed between diseased and control tissues across several key fluorophores. The machine learning classifier achieved high prediction accuracy using both the Operetta CLS system (90.38 %) and a custom-modified Olympus IX83 platform (83.28 %) during 10-fold cross-validation, and the false-color prediction maps showed strong agreement with histological assessments. These results highlight new perspectives on LSCD through the characterization of autofluorescent biomarkers and demonstrate the feasibility of AFMI as a diagnostic tool in a mouse model, providing a basis for future investigations into its possible adaptation for non-invasive clinical assessment of LSCD and other ocular surface disorders.

诊断角膜缘干细胞缺乏症（LSCD）仍然具有挑战性，本研究评估了新开发的自体荧光多光谱成像（AFMI）技术的诊断潜力。本研究采用36只小鼠未染色的固定角膜横切面。这些小鼠的右眼患有碱诱导的LSCD，而左眼作为健康对照。通过多个光谱通道获得角膜上皮的自体荧光多光谱图像，以跟踪内源性荧光团光谱的变化。应用大数据分析和机器学习分类器区分受lscd影响的组织和健康组织。通过组织学评价评价该技术的性能。在用于研究应用的Operetta CLS （Perkin Elmer）和用于潜在临床翻译的定制改进的Olympus IX83系统上进行成像。自体荧光信号强度的显著差异(p

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引用次数: 0

Investigation of the biomechanical changes at the iris-lens interface after vitrectomy with silicone oil tamponade: Insights from ultrasound biomicroscopy 硅油填塞玻璃体切除术后虹膜-晶状体界面生物力学变化的超声生物显微镜观察

IF 2.7 2区医学 Q1 OPHTHALMOLOGY

Experimental eye research

Pub Date : 2026-03-01 Epub Date: 2026-01-07 DOI: 10.1016/j.exer.2026.110855

Jiajun Chen, Ling Wang, Long Tao, Shasha Xue, Yunxiao Wang, Fenglei Wang

This prospective cohort study investigated anterior segment biomechanical alterations and lens stability using ultrasound biomicroscopy (UBM) in 60 eyes (58 patients) undergoing pars plana vitrectomy (PPV) with silicone oil (SO) tamponade for rhegmatogenous (18 eyes) or diabetic tractional retinal detachment (42 eyes). UBM parameters, including central corneal thickness (CCT), anterior chamber depth (ACD), lens vault (LV), angle-opening distance (AOD500), trabecular-iris angle (TIA), iris-lens angle (ILA), and iris-lens contact distance (ILCD), were assessed preoperatively and 3 months postoperatively. Significant postoperative reductions were observed in CCT (−0.026 mm, P = 0.005), superior ILCD (0.921→0.730 mm, P = 0.006), inferior ILCD (0.914→0.702 mm, P = 0.002), and mean ILCD (0.947→0.745 mm, P = 0.001). The inferior ILA increased (20.31°→23.39°, P = 0.032), while the temporal ILA decreased (20.70°→18.29°, P = 0.047). Subgroup analysis comparing normotensive and hypertensive eyes revealed significant differences in nasal ΔILA (P = 0.008) and temporal ΔILCD (P = 0.014). Multiple regression identified a negative correlation between intraocular pressure (IOP) and nasal ΔILA (β = −0.353, P = 0.002). The findings demonstrate that PPV with SO tamponade induces significant biomechanical alterations at the iris-lens interface, compromising lens stability, and provide valuable anatomical insights for optimizing cataract surgery in SO-filled eyes.

本前瞻性队列研究采用超声生物显微镜（UBM）观察60眼（58例）玻璃体切割术（PPV）加硅油（SO）压塞治疗孔源性（18眼）或糖尿病牵引性视网膜脱离（42眼）的前段生物力学改变和晶状体稳定性。术前和术后3个月评估UBM参数，包括角膜中央厚度（CCT）、前房深度（ACD）、晶状体穹窿（LV）、角开口距离（AOD500）、小梁-虹膜角（TIA）、虹膜-晶状体角（ILA）、虹膜-晶状体接触距离（ILCD）。术后CCT （- 0.026 mm, P = 0.005）、上ILCD（0.921→0.730 mm, P = 0.006）、下ILCD（0.914→0.702 mm, P = 0.002）、平均ILCD（0.947→0.745 mm, P = 0.001）均显著降低。下侧ILA增大（20.31°→23.39°，P = 0.032），颞侧ILA减小（20.70°→18.29°，P = 0.047）。亚组分析结果显示，正常眼和高血压眼的鼻部ΔILA （P = 0.008）和颞部ΔILCD （P = 0.014）差异有统计学意义。多元回归发现眼压（IOP）与鼻腔ΔILA呈负相关（β = - 0.353, P = 0.002）。研究结果表明，有SO填塞的PPV在虹膜-晶状体界面引起了显著的生物力学改变，影响了晶状体的稳定性，并为优化SO填充眼的白内障手术提供了有价值的解剖学见解。

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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 : 2026-03-01 Epub 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

IF 2.7 2区医学 Q1 OPHTHALMOLOGY

Experimental eye research

Pub Date : 2026-03-01 Epub Date: 2025-12-29 DOI: 10.1016/j.exer.2025.110834

Xinyao Han , Tiexi Wu , Wenyi Si , Lu Zhang , Shiyu Jiang , Suxia Liu , Xuejiao Qin

Tumor necrosis factor-α-induced protein 8-like 2 (TNFAIP8L2/TIPE2) is a critical regulator of immune and inflammatory responses. Although its roles in diabetic retinopathy and choroidal neovascularization have been reported, its influence on the natural state of retina remains unclear. This study investigated whether TIPE2 knockout alone affects retinal structure and function. Wild-type (WT) and TIPE2^−/− mice were categorized into juvenile, adult, and late middle-aged groups. Retinal lamellar thickness and blood perfusion across 17 regions were quantified using ultra-widefield swept-source optical coherence tomography and angiography (SS-OCT/OCTA). Generalized estimating equations (GEE) were applied to account for within-eye correlations and to test main effects of genotype and age. Genotype showed a significant main effect on superficial vascular plexus (Svp) perfusion, indicating overall lower Svp perfusion in TIPE2^−/− mice, whereas no significant main effects were detected for deep vascular plexus (Dvp) perfusion. TIPE2^−/− mice also exhibited reduced total retinal thickness, with the strong genotype-associated thinning observed in the inner nuclear layer (INL), inner plexiform layer (IPL), outer plexiform layer (OPL) and outer nuclear layer (ONL). Age exerted smaller effects, showing a significant main effect on total retinal thickness and retinal pigment epithelium (RPE) thickness. Pan-lactylation levels in retinal tissue were assessed by Western Blot and markedly upregulated in adult TIPE2^−/− retinas. These findings demonstrate that TIPE2 deficiency was associated with retina hypoperfusion and age-related retinal thinning, suggesting that TIPE2 plays an essential role in preserving the natural state of retina.

肿瘤坏死因子-α-诱导的蛋白8-样2 （TNFAIP8L2/TIPE2）是免疫和炎症反应的关键调节因子。虽然其在糖尿病视网膜病变和脉络膜新生血管中的作用已被报道，但其对视网膜自然状态的影响尚不清楚。本研究探讨单独敲除TIPE2是否会影响视网膜结构和功能。野生型（WT）和TIPE2-/-小鼠分为幼年组、成年组和中老年组。采用超宽视场扫描源光学相干断层扫描和血管造影（SS-OCT/OCTA）对17个区域的视网膜板层厚度和血流灌注进行量化。应用广义估计方程（GEE）来解释眼内相关性，并检验基因型和年龄的主要影响。基因型对TIPE2-/-小鼠的浅血管丛（Svp）灌注有显著的主要影响，表明TIPE2-/-小鼠的Svp灌注总体降低，而对深血管丛（Dvp）灌注无显著的主要影响。TIPE2-/-小鼠也表现出视网膜总厚度的减少，在内核层（INL）、内丛状层（IPL）、外丛状层（OPL）和外核层（ONL）观察到强烈的基因型相关变薄。年龄的影响较小，主要影响视网膜总厚度和视网膜色素上皮（RPE）厚度。Western Blot检测视网膜组织中泛乳酸化水平，发现成人TIPE2-/-视网膜中泛乳酸化水平明显上调。这些发现表明，TIPE2缺乏与视网膜灌注不足和年龄相关性视网膜变薄有关，提示TIPE2在保持视网膜自然状态中起重要作用。

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引用次数: 0

Commentary on “A sustainable tissue-specific hydrogel from decellularized corneal ECM for 3D in vitro ocular models” by Santos et al. Santos等人对“一种来自脱细胞角膜ECM的可持续组织特异性水凝胶用于体外3D眼模型”的评论。

IF 2.7 2区医学 Q1 OPHTHALMOLOGY

Experimental eye research

Pub Date : 2026-03-01 Epub Date: 2025-12-28 DOI: 10.1016/j.exer.2025.110833

Abhisarika Maduri , Rohit Saxena , Varshini Vadhithala , Sachin Kumar

引用次数: 0

Layer-by-layer coated chitosan-CRISPR/Cas9 mTOR nanoparticles: A novel approach to inhibit lens epithelial cell proliferation and migration for preventing posterior capsule opacification 壳聚糖- crispr /Cas9 mTOR纳米颗粒：一种抑制晶状体上皮细胞增殖和迁移以防止后囊膜混浊的新方法

IF 2.7 2区医学 Q1 OPHTHALMOLOGY

Experimental eye research

Pub Date : 2026-03-01 Epub Date: 2025-12-26 DOI: 10.1016/j.exer.2025.110828

Chen Chang , Jiaming Yang , Ziming Liu , Jiayu Chen , Biying Wang , Junqi Li , Hongling Liu

Posterior capsular opacification (PCO) is the most common complication following cataract surgery and a significant cause of vision impairment. PCO arises from the proliferation, migration, and epithelial-mesenchymal transition (EMT) of residual lens epithelial cells (LECs), driven by an activated mTOR signalling pathway. Previous research has demonstrated that inhibiting mTOR activity effectively reduces LEC proliferation and EMT in rabbit models. However, achieving sustained mTOR inhibition remains a challenge.

In this study, we encapsulated the CRISPR/Cas9 system targeting mTOR into chitosan nanoparticles (Chi-gRNA) with an average size of 135 nm. These nanoparticles exhibited resistance to DNase I digestion. To prolong release duration, we incorporated these Chi-gRNA nanoparticles onto the surface of intraocular lenses (IOLs) via layer-by-layer (LbL) assembly. The LbL coatings consisted of alternating layers of positively charged polyethyleneimine (PEI) and negatively charged heparin, interspersed with Chi-gRNA nanoparticles over five consecutive cycles.

Spectral analysis confirmed the successful integration and coating of nanoparticles, with characteristic peaks validating the electrostatic assembly of the layers. In vitro assays demonstrated that Chi-gRNA-coated IOLs significantly inhibited the proliferation, migration, and adhesion of human lens epithelial cells (hLECs).

These findings highlight the potential of LbL-coated IOLs to deliver CRISPR/Cas9 system-targeting mTOR nanoparticles as a novel and effective strategy to prevent PCO in patients undergoing cataract surgery. This approach offers a promising avenue for the long-term management of this prevalent postoperative complication.

后囊膜混浊（PCO）是白内障手术后最常见的并发症，也是视力受损的重要原因。残晶状体上皮细胞（LECs）的增殖、迁移和上皮-间质转化（EMT）由激活的mTOR信号通路驱动。先前的研究表明，抑制mTOR活性可有效降低兔模型中LEC增殖和EMT。然而，实现持续的mTOR抑制仍然是一个挑战。在这项研究中，我们将靶向mTOR的CRISPR/Cas9系统封装在平均尺寸为135 nm的壳聚糖纳米颗粒（Chi-gRNA）中。这些纳米颗粒表现出对dna酶I消化的抵抗力。为了延长释放时间，我们将这些Chi-gRNA纳米颗粒通过逐层组装（LbL）结合到人工晶状体（iol）表面。LbL涂层由带正电荷的聚乙烯亚胺（PEI）和带负电荷的肝素交替层组成，并在连续五个循环中点缀Chi-gRNA纳米颗粒。光谱分析证实了纳米粒子的成功集成和涂层，特征峰证实了层的静电组装。体外实验表明，chi - grna包被的iol可显著抑制人晶状体上皮细胞（hLECs）的增殖、迁移和粘附。这些发现强调了lbl涂层iol递送CRISPR/Cas9系统靶向mTOR纳米颗粒作为一种新的有效策略来预防白内障手术患者的PCO的潜力。这种方法为这种常见的术后并发症的长期治疗提供了一条有希望的途径。

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