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Heightened visual light sensitivity discomfort measured by the ocular photosensitivity analyzer is associated with chronic ocular pain 眼光敏度分析仪测量的视光敏度升高的不适与慢性眼痛有关
IF 5.9 1区 医学 Q1 OPHTHALMOLOGY Pub Date : 2025-06-19 DOI: 10.1016/j.jtos.2025.06.007
Ema V. Karakoleva , Nicholas Pondelis , Cameron Talbert , Mariela C. Aguilar , Alex Gonzalez , Cornelis Rowaan , Heather Durkee , Paula A. Sepulveda-Beltran , David Valdes-Arias , Chloe Shields , Shreya Bhatt , David Zurakowski , Deborah S. Jacobs , Joseph B. Ciolino , Elizabeth R. Felix , Jean-Marie Parel , Eric A. Moulton , Anat Galor

Purpose

To quantify visual photosensitivity discomfort thresholds (VPDT) in individuals with chronic ocular pain (COP) compared to controls without COP and explore relationships between VPDT, demographics, clinical factors, and ocular metrics.

Methods

Prospective case-control study of 75 participants: 36 with COP (age 46.5 ± 15.6 years; 56 % female) and 39 controls (39.2 ± 15.6 years; 56 % female). COP was defined by self-reported ocular pain intensity ≥15 on a numerical rating scale (range, 0–100) for ≥3 months. COP cases were subclassified into inflammatory (Sjögren's disease) and neuropathic ocular pain subgroups. VPDT was measured using the Ocular Photosensitivity Analyzer (OPA), and ocular symptoms were assessed using the Visual Light Sensitivity Questionnaire (VLSQ-8; 8–40) and Ocular Surface Disease Index (OSDI; 0–100), with OSDI Question 1 addressing light sensitivity (OSDI-Q1; 0–4).

Results

COP patients exhibited lower VPDT than controls (log lux, 1.60 ± 1.17 vs. 2.42 ± 1.05; P = 0.006), indicating greater photosensitivity discomfort. No differences in VPDT were seen across COP subtypes. COP patients also reported greater symptom severity than controls, with higher VLSQ-8 (21.92 ± 1.41 vs. 9.03 ± 0.53), OSDI (50.84 ± 3.88 vs. 2.82 ± 0.85), and OSDI-Q1 (2.00 ± 0.24 vs. 0.14 ± 0.06) scores (all P < 0.001). VPDT negatively correlated with VLSQ-8 (ρ = −0.75) and OSDI-Q1 (ρ = −0.62), demonstrating alignment between subjective light sensitivity symptoms and OPA-measured photosensitivity discomfort. Multivariable regression identified fibromyalgia as the strongest predictor of VPDT (19.6 % variance explained), with chronic fatigue improving the model (26.5 %).

Conclusion

COP subjects display greater photosensitivity-related discomfort than controls, highlighting the OPA's potential as a psychophysical tool for quantifying photoallodynia. Further research is needed to assess its diagnostic utility across COP subtypes.
量化慢性眼痛(COP)患者的视觉光敏性不适阈值(VPDT),并与无COP的对照组进行比较,探讨VPDT、人口统计学、临床因素和眼部指标之间的关系。
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引用次数: 0
Attribution of causality in Stevens-Johnson syndrome/toxic epidermal necrolysis 史蒂文斯-约翰逊综合征/中毒性表皮坏死松解症的因果关系归因
IF 5.9 1区 医学 Q1 OPHTHALMOLOGY Pub Date : 2025-06-18 DOI: 10.1016/j.jtos.2025.06.004
Asha Parvathaneni , Liliya Benchetrit , Derek Metcalfe , James T. Kwan , Yandong Bian , Tavé Van Zyl , Hajirah N. Saeed , James Chodosh
Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) is an acute, severe immunobullous disorder of skin and mucous membranes that is most commonly induced by exposure to drugs. Causation of SJS/TEN is most often determined by the “algorithm of drug causality for epidermal necrolysis” (ALDEN) tool. However, concerns remain regarding the precision of ALDEN and causality assessment tools, potentially impacting ongoing studies attempting to link specific genotypes with specific drug classes as causes. To determine whether a standard of care exists in attribution of causation in SJS/TEN, we performed a narrative review of current concepts on causation in SJS/TEN, and available clinical and laboratory assessment tools for attributing causation. We found that current SJS/TEN causality attribution tools, including ALDEN, are somewhat limited by underlying assumptions. The utility of ex vivo tests proposed for determining causation in SJS/TEN, specifically the lymphocyte transformation test and cytokine stimulation assays, remain under investigation and are either not tractable for acute SJS/TEN or are not yet validated. In summary, a critical unmet need exists in the care of SJS/TEN patients, namely the difficulty in determining a precise cause in any specific individual. This shortfall limits the clinician's ability to discontinue only the causal agent in the acute phase, confounds studies of pathogenesis, and leaves affected patients in the chronic phase without knowing which drug or drug class is safe to use in the future. Further studies are needed to close this critical gap in the care of this devastating disease.
史蒂文斯-约翰逊综合征/中毒性表皮坏死松解症(SJS/TEN)是一种急性、严重的皮肤和粘膜免疫大泡性疾病,最常由药物暴露引起。SJS/TEN的病因通常由“表皮坏死松解药物因果关系算法”(ALDEN)工具确定。然而,人们仍然关注ALDEN的准确性和因果关系评估工具,这可能会影响正在进行的试图将特定基因型与特定药物类别作为病因联系起来的研究。为了确定在SJS/TEN的因果归因中是否存在谨慎标准,我们对SJS/TEN的因果关系的当前概念以及用于归因的现有临床和实验室评估工具进行了叙述性回顾。我们发现目前的SJS/TEN因果归因工具,包括ALDEN,在某种程度上受到潜在假设的限制。用于确定SJS/TEN病因的离体试验,特别是淋巴细胞转化试验和细胞因子刺激试验,仍在研究中,要么不适用于急性SJS/TEN,要么尚未得到验证。总之,在SJS/TEN患者的护理中存在一个关键的未满足需求,即难以确定任何特定个体的确切病因。这一缺陷限制了临床医生在急性期仅停用致病因子的能力,混淆了发病机制的研究,并使受影响的患者处于慢性期,而不知道将来使用哪种药物或药物类别是安全的。需要进一步的研究来缩小这一毁灭性疾病护理方面的这一重大差距。
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引用次数: 0
A pilot randomized controlled trial of topical androgen treatment in dry eye 局部雄激素治疗干眼症的随机对照试验
IF 5.9 1区 医学 Q1 OPHTHALMOLOGY Pub Date : 2025-06-14 DOI: 10.1016/j.jtos.2025.06.002
Jay Ruzhang Jiang , Rima Khankan , William H. Ridder III , Andrew Loc Nguyen , Jerry R. Paugh

Purpose

To evaluate the safety and efficacy of eyelid androgen gel application to treat moderate to severe dry eye disease.

Methods

Twenty four eyes of 24 subjects (12 eyes per arm) were randomized to either eyelid testosterone or vehicle gel. Subjects received either 17β-Hydroxyandrost-4-en-3-one) 4.5 % wt./wt. or vehicle gel, applied twice daily 12 h apart for 4 weeks. Outcome parameters were monitored at 2-, and 4-weeks during dosing, and at 4-, and 8-weeks following dosing cessation.

Results

Significant positive differences were found in the androgen arm only, for Schein symptom score, tear meniscus height (TMH), fluorescein tear breakup time (fTBUT) and meibum score (repeated ANOVA, all p = 0.046 or less for each arm comparison) at all follow-up visits compared to baseline. For example, fTBUT in the androgen arm at 4 weeks was 6.2 ± 1.5 s compared to baseline, 3.3 ± 0.9 secs p< 0.001 (Dunnett's test, 95 % CI [1.838, 3.829]). No change was observed for either arm for staining, tear osmolarity, OSDI, non-invasive breakup time (NIBUT), serum lipid levels or hematocrit. Serum testosterone increased ∼ 9-fold in females (paired t-test; p = 0.006; CI [-240.2, −55.6]) in the androgen arm, but not males (paired t-test; p = 0.727; CI [-25.9, 31.2]).

Conclusions

Eyelid androgen gel application, 4.5 % wt./wt., was effective in improving tear fTBUT, symptoms, TMH and meibomian secretion grade in dry eye patients. Future research requires a larger sample size, outcome measure variability reduction and formulation optimization for absorption, androgen type, and dosing regimen.
目的评价眼睑雄激素凝胶治疗中重度干眼病的安全性和有效性。
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引用次数: 0
Association of tobacco smoking with aqueous deficient and evaporative dry eye disease subtypes: a prospective registry-based case-control study 吸烟与水分缺乏性和蒸发性干眼病亚型的关系:一项前瞻性登记病例对照研究
IF 5.9 1区 医学 Q1 OPHTHALMOLOGY Pub Date : 2025-06-13 DOI: 10.1016/j.jtos.2025.06.001
Barry Power , Michael T.M. Wang , Ally L. Xue , Jennifer P. Craig
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引用次数: 0
Transcriptional landscape of aniridia-associated keratopathy through single-cell RNA sequencing 通过单细胞RNA测序研究无虹膜相关性角膜病变的转录景观
IF 5.9 1区 医学 Q1 OPHTHALMOLOGY Pub Date : 2025-06-03 DOI: 10.1016/j.jtos.2025.05.008
Masahito Yoshihara , Rei Kamuro , Susumu Hara , Nozomi Nishida , Koji Ohmoto , Yuzuru Sasamoto , Satoshi Kawasaki , Yoshinori Oie , Kohji Nishida

Purpose

Aniridia-associated keratopathy (AAK) is a progressive condition characterized by conjunctivalization of the cornea, yet its molecular mechanisms remain largely unknown. This study aims to elucidate the transcriptional landscape of AAK by characterizing the gene expression profiles of corneal epithelial cells in a patient with congenital aniridia.

Methods

Single-cell RNA sequencing (scRNA-seq) was performed on epithelial tissues collected from the clear central corneal region and limbus of a 48-year-old female patient with congenital aniridia. The transcriptomic profiles were compared with those of healthy control samples.

Results

scRNA-seq analysis revealed that a subpopulation of cells from the clear central corneal region expressed the cornea-specific keratins KRT3 and KRT12 despite a significant reduction in PAX6 expression. These cells exhibited corneal, conjunctival, or mixed gene signatures. Genes associated with wound healing and apoptosis were upregulated in the cornea-like cells from the aniridic cornea, indicating a chronic wound healing state. Elevated KLF4 expression and regulon activity were observed in these cornea-like cells. Most limbal epithelial cells exhibited conjunctiva-like characteristics, reflecting a loss of limbal cell identity.

Conclusion

While acknowledging the limitations of a single case study, this study provides deeper insights into the transcriptional signatures associated with AAK using scRNA-seq. We identified transcriptional alterations reflecting AAK progression and highlighted potential transcription factors that may contribute to corneal identity maintenance despite PAX6 deficiency. These findings enhance our understanding of AAK and suggest potential therapeutic strategies to slow its progression.
目的无虹膜相关性角膜病变(AAK)是一种以角膜结膜炎为特征的进行性疾病,其分子机制在很大程度上仍不清楚。本研究旨在通过表征先天性无虹膜患者角膜上皮细胞的基因表达谱来阐明AAK的转录景观。方法对48岁女性先天性无虹膜患者角膜中央透明区及角膜缘上皮组织进行单细胞RNA测序(scRNA-seq)。将转录组谱与健康对照样本进行比较。结果scrna -seq分析显示,尽管PAX6表达显著降低,但来自角膜中央区域的一个细胞亚群表达了角膜特异性角蛋白KRT3和KRT12。这些细胞表现出角膜、结膜或混合基因特征。无角膜样角膜细胞中与伤口愈合和凋亡相关的基因上调,表明伤口愈合处于慢性状态。在这些角膜样细胞中观察到KLF4表达和调控蛋白活性升高。大多数角膜缘上皮细胞表现出结膜样特征,反映了角膜缘细胞身份的丧失。虽然承认单个案例研究的局限性,但本研究使用scRNA-seq对与AAK相关的转录特征提供了更深入的了解。我们发现了反映AAK进展的转录改变,并强调了尽管PAX6缺乏,但可能有助于角膜身份维持的潜在转录因子。这些发现增强了我们对AAK的理解,并提出了减缓其进展的潜在治疗策略。
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引用次数: 0
Topical duloxetine for treatment of corneal keratinization in Aniridia-Associated Keratopathy 局部度洛西汀治疗无虹膜相关性角膜病变的角膜角化。
IF 5.9 1区 医学 Q1 OPHTHALMOLOGY Pub Date : 2025-05-31 DOI: 10.1016/j.jtos.2025.05.011
Marcel Y. Avila , Mario A. Jimenez-Mora , Edgar M. Espana
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引用次数: 0
Fenofibrate ameliorates ocular surface inflammation in diabetic keratopathy 非诺贝特改善糖尿病性角膜病变的眼表炎症
IF 5.9 1区 医学 Q1 OPHTHALMOLOGY Pub Date : 2025-05-30 DOI: 10.1016/j.jtos.2025.05.010
Hassan Mansoor , Isabelle Xin Yu Lee , Chang Liu , Mingyi Yu , Charmaine Jan Li Toh , Victor Wei-Tsu Hsu , Fengyi Liu , Daqian Lu , Thomas Chuen Lam , Hong Chang Tan , Lei Zhou , Yu-Chi Liu

Purpose

To investigate the efficacy of oral fenofibrate in the amelioration of ocular surface inflammation in diabetes mellitus (DM).

Methods

In this open-label interventional study, 41 participants with type 2 DM received oral fenofibrate for 30 days. Forty age-matched healthy controls were recruited. Ocular surface objective and subjective assessment, in-vivo confocal microscopy (IVCM) imaging and quantification for corneal dendritic cells (DCs), epithelium and neuromas were performed. Tear inflammatory markers and proteomics were analyzed with enzyme-linked immunosorbent assay (ELISA) and Data Independent Acquisition experiments before and after treatment.

Results

Oral fenofibrate treatment significantly improved tear film breakup time (p = 0.004), corneal staining evaluated with National Eye Institute-Corneal Fluorescein Staining scores (p = 0.005), and ocular surface symptoms assessed with the Ocular Surface Disease Index scores (p = 0.003), in DM patients. On IVCM, fenofibrate significantly reduced mean DC area (p = 0.01) and mean DC density (p = 0.02), while increasing mean DC elongation (p = 0.004) and length (p = 0.01), suggesting less DC activities. Fenofibrate also significantly increased corneal epithelial cell density (p = 0.04). 192 tear proteins were significantly altered after treatment. Fenofibrate significantly up-regulated the expression of anti-inflammatory interleukin-1 receptor antagonist, while significantly reduced the concentrations of pro-inflammatory and inflammatory proteins, including tumour necrosis factor α, nuclear factor kappa B, complement 4 B, cytochrome B5 Type A, and cytochrome B5 Type B (all p < 0.05) in tears, via regulation of tricarboxylic acid cycle, oxidative phosphorylation and liver X receptor/retinoid X receptor activation.

Conclusion

This first clinical trial demonstrated that oral fenofibrate ameliorates diabetic ocular surface inflammation, providing a novel therapeutic option for diabetic keratopathy.
目的观察非诺贝特口服治疗糖尿病(DM)眼表炎症的疗效。方法在这项开放标签的干预性研究中,41名2型糖尿病患者口服非诺贝特30天。招募了40名年龄匹配的健康对照。进行眼表客观和主观评价,角膜树突状细胞(dc)、上皮和神经瘤的体内共聚焦显微镜(IVCM)成像和定量。采用酶联免疫吸附试验(ELISA)和数据独立采集实验分析治疗前后泪液炎症标志物和蛋白质组学。结果非诺贝特治疗可显著改善糖尿病患者泪膜破裂时间(p = 0.004)、美国国家眼科研究所角膜荧光素染色评分评估角膜染色(p = 0.005)和眼表疾病指数评分评估眼表症状(p = 0.003)。在IVCM上,非诺贝特显著降低了平均DC面积(p = 0.01)和平均DC密度(p = 0.02),增加了平均DC伸长(p = 0.004)和长度(p = 0.01),表明DC活性降低。非诺贝特还显著增加了角膜上皮细胞密度(p = 0.04)。192个泪液蛋白在治疗后显著改变。非诺贝特显著上调抗炎白介素-1受体拮抗剂的表达,同时显著降低促炎和炎症蛋白的浓度,包括肿瘤坏死因子α、核因子κ B、补体4b、细胞色素B5 A型和细胞色素B5 B型(均p <;0.05),通过调节三羧酸循环、氧化磷酸化和肝脏X受体/类视黄醇X受体激活。结论首次临床试验表明,口服非诺贝特可改善糖尿病性眼表炎症,为糖尿病性角膜病变提供了一种新的治疗选择。
{"title":"Fenofibrate ameliorates ocular surface inflammation in diabetic keratopathy","authors":"Hassan Mansoor ,&nbsp;Isabelle Xin Yu Lee ,&nbsp;Chang Liu ,&nbsp;Mingyi Yu ,&nbsp;Charmaine Jan Li Toh ,&nbsp;Victor Wei-Tsu Hsu ,&nbsp;Fengyi Liu ,&nbsp;Daqian Lu ,&nbsp;Thomas Chuen Lam ,&nbsp;Hong Chang Tan ,&nbsp;Lei Zhou ,&nbsp;Yu-Chi Liu","doi":"10.1016/j.jtos.2025.05.010","DOIUrl":"10.1016/j.jtos.2025.05.010","url":null,"abstract":"<div><h3>Purpose</h3><div>To investigate the efficacy of oral fenofibrate in the amelioration of ocular surface inflammation in diabetes mellitus (DM).</div></div><div><h3>Methods</h3><div>In this open-label interventional study, 41 participants with type 2 DM received oral fenofibrate for 30 days. Forty age-matched healthy controls were recruited. Ocular surface objective and subjective assessment, in-vivo confocal microscopy (IVCM) imaging and quantification for corneal dendritic cells (DCs), epithelium and neuromas were performed. Tear inflammatory markers and proteomics were analyzed with enzyme-linked immunosorbent assay (ELISA) and Data Independent Acquisition experiments before and after treatment.</div></div><div><h3>Results</h3><div>Oral fenofibrate treatment significantly improved tear film breakup time (p = 0.004), corneal staining evaluated with National Eye Institute-Corneal Fluorescein Staining scores (p = 0.005), and ocular surface symptoms assessed with the Ocular Surface Disease Index scores (p = 0.003), in DM patients. On IVCM, fenofibrate significantly reduced mean DC area (p = 0.01) and mean DC density (p = 0.02), while increasing mean DC elongation (p = 0.004) and length (p = 0.01), suggesting less DC activities. Fenofibrate also significantly increased corneal epithelial cell density (p = 0.04). 192 tear proteins were significantly altered after treatment. Fenofibrate significantly up-regulated the expression of anti-inflammatory interleukin-1 receptor antagonist, while significantly reduced the concentrations of pro-inflammatory and inflammatory proteins, including tumour necrosis factor α, nuclear factor kappa B, complement 4 B, cytochrome B5 Type A, and cytochrome B5 Type B (all p &lt; 0.05) in tears, via regulation of tricarboxylic acid cycle, oxidative phosphorylation and liver X receptor/retinoid X receptor activation.</div></div><div><h3>Conclusion</h3><div>This first clinical trial demonstrated that oral fenofibrate ameliorates diabetic ocular surface inflammation, providing a novel therapeutic option for diabetic keratopathy.</div></div>","PeriodicalId":54691,"journal":{"name":"Ocular Surface","volume":"38 ","pages":"Pages 31-40"},"PeriodicalIF":5.9,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144195330","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
Safety of subconjunctival injection of mesenchymal stromal cells in persistent corneal epithelial disease – A phase 1b clinical trial 结膜下注射间充质间质细胞治疗持续性角膜上皮疾病的安全性- 1b期临床试验
IF 5.9 1区 医学 Q1 OPHTHALMOLOGY Pub Date : 2025-05-23 DOI: 10.1016/j.jtos.2025.05.009
Grace C. Tu , Farshad Abedi , Arthur Y. Chang , Xiang Shen , Mohammad Soleimani , Iskra Araujo , Rebecca Jung , Jeonghyun Kwon , Khandeker N. Anwar , Zohreh Arabpour , Nadim Mahmud , Elmer Y. Tu , Reza Dana , Peiman Hematti , Charlotte E. Joslin , Ali R. Djalilian

Purpose

To investigate the safety and tolerability of subconjunctival injection of three escalating doses of allogeneic bone marrow-derived mesenchymal stromal cells (MSCs) in patients with persistent corneal epithelial defect/disease (PCED).

Design

Prospective single-center open label phase 1b clinical trial.

Participants

Patients with PCED in the setting of neurotrophic keratitis and/or limbal stem cell deficiency.

Methods

A dose escalation study design was used. The first three patients received a subconjunctival injection of 1 × 106 MSCs/50 μL suspension; subsequently, three participants were treated with 1 subconjunctival injection of 3 × 106 MSCs/150 μL; and two participants received 2 subconjunctival injections of 3 × 106 MSCs/150 μl in 2 conjunctival sites.

Main outcome measures

The primary outcome was the safety of the treatment determined on day 28 post-injection. Ocular surface toxicity and other ocular or systemic treatment emergent adverse events (TEAEs) were assessed at 1, 7, 14, 28 and 90 days. Demonstration of safety on day 28 was required before escalating to the next higher dose. Changes in the PCED were also monitored.

Results

Eight participants completed the 90-day study. All 3 doses of subconjunctival MSCs were well tolerated. No participant developed ocular surface toxicity or other ocular or systemic TEAEs. The size of the PCED improved in 5 (63 %) patients; it increased in 2 (25 %) patients; and no progressive improvement was observed with dose escalation.

Conclusion

Subconjunctival administration of MSCs was safe and well tolerated with no systemic or ocular toxicity in patients with PCED. Improvement in epithelial defect size was observed in 63 % of the participants.
目的:探讨三种递增剂量的同种异体骨髓间充质间质细胞(MSCs)在持续性角膜上皮缺损/疾病(PCED)患者结膜下注射的安全性和耐受性。设计:前瞻性单中心开放标签1b期临床试验。参与者:神经营养性角膜炎和/或角膜缘干细胞缺乏的PCED患者。方法:采用剂量递增研究设计。前3例患者在结膜下注射1 × 106个MSCs/50 μL悬液;随后,3名受试者接受1次结膜下注射3 × 106个MSCs/150 μL;2例患者在2个结膜部位注射3 × 106个MSCs/150μl。主要观察指标:主要观察指标为注射后第28天确定的治疗安全性。在第1、7、14、28和90天评估眼表毒性和其他眼部或全身治疗紧急不良事件(teae)。需要在第28天进行安全性证明,然后再进行下一个更高的剂量。还监测了PCED的变化。结果:8名参与者完成了为期90天的研究。所有3种剂量的结膜下MSCs均耐受良好。没有参与者发生眼表毒性或其他眼部或全身teae。5例(63%)患者PCED大小改善;2例(25%)患者升高;随着剂量的增加,没有观察到进行性改善。结论:在PCED患者中,结膜下给药MSCs是安全且耐受性良好的,无全身或眼部毒性。在63%的参与者中观察到上皮缺陷大小的改善。
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引用次数: 0
MicroRNAs in corneal Diseases: Emerging roles as biomarkers, regulators, and therapeutics microrna在角膜疾病中的作用:生物标志物、调节因子和治疗方法。
IF 5.9 1区 医学 Q1 OPHTHALMOLOGY Pub Date : 2025-05-22 DOI: 10.1016/j.jtos.2025.05.007
Liangbo Chen , Shiding Li , Yao Fu
MicroRNAs (miRNAs) are conserved, short, non-coding RNAs that play a crucial role in regulating gene expression. Emerging evidence suggests that miRNAs are closely involved in the pathophysiology of various corneal diseases, particularly in regulating corneal wound healing, inflammation and neovascularization. In this review, we summarized the recent progress of miRNAs in corneal diseases, especially focused on their application as diagnostic biomarkers, regulators of cell biology, and therapeutic targets. Recent advances in miRNA detection technology have made it possible to analyze minimal miRNAs in samples such as tears or exosomes, further enhancing the ability to identify disease-specific miRNA profiles and providing potential objective indicators for the early diagnosis of disease. Meanwhile, we summarized the mechanisms and pathways of multiple miRNAs in regulating various biological processes of corneal cells, as well as the advantages of studying miRNA compared to proteins or genes. Furthermore, we explore the potential of miRNAs-based therapies, especially introduce various miRNA delivery systems and challenges associated with clinical translation. This review highlights the need for further research to harness the full potential of miRNAs in treating various corneal diseases.
MicroRNAs (miRNAs)是一种保守的、短的非编码rna,在调节基因表达中起着至关重要的作用。越来越多的证据表明,mirna密切参与各种角膜疾病的病理生理,特别是在调节角膜伤口愈合、炎症和新生血管方面。本文综述了近年来mirna在角膜疾病中的研究进展,重点介绍了其在角膜疾病诊断标志物、细胞生物学调节因子和治疗靶点等方面的应用。miRNA检测技术的最新进展使得分析眼泪或外泌体等样品中的最小miRNA成为可能,进一步增强了识别疾病特异性miRNA谱的能力,并为疾病的早期诊断提供了潜在的客观指标。同时,我们总结了多种miRNA调控角膜细胞各种生物过程的机制和途径,以及研究miRNA相对于蛋白质或基因的优势。此外,我们探索了基于miRNA的治疗的潜力,特别是介绍了各种miRNA传递系统和与临床转化相关的挑战。这篇综述强调了需要进一步研究以充分利用mirna在治疗各种角膜疾病中的潜力。
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引用次数: 0
Tear fluid derived extracellular vesicles for new biomarker discovery 泪液衍生的细胞外囊泡:发现新的生物标志物。
IF 5.9 1区 医学 Q1 OPHTHALMOLOGY Pub Date : 2025-05-12 DOI: 10.1016/j.jtos.2025.05.001
Natalie Phan , Yi Li , Menglu Yang , Fei Liu
Various cell types release extracellular vesicles (EVs) containing proteins, DNA, and RNA essential for intercellular communication. The bioactive molecules from EVs can reflect disease status and monitor progression, while their communication abilities suggest therapeutic potential. We will review various EV isolation methods, EV-enriched fluids, and studies analyzing differential mi-RNA and protein levels extracted from EVs. Specifically, tear-derived EVs, which protect their molecular content and allow for real-time monitoring of ocular conditions such as Dry Eye Disease (DED), Sjögren's disease (SJD), Ocular graft-versus-host disease (oGVHD), and Diabetic Retinopathy (DR), which all currently remain undiagnosed in patients. EVs also provide potential as carriers for gene transfer, and mesenchymal stem cell (MSCs)-derived EVs are shown to be immunomodulatory, demonstrating promise for autoimmune ocular diseases. Through the multi-omic analysis of tear-fluid content, EVs are promising biomarkers and therapeutic agents in ocular diseases.
不同类型的细胞释放细胞外囊泡(EVs),其中含有细胞间通讯所必需的蛋白质、DNA和RNA。来自ev的生物活性分子可以反映疾病状态和监测进展,而它们的交流能力表明了治疗潜力。我们将回顾各种EV分离方法,EV富集液,以及分析从EV中提取的差异mi-RNA和蛋白质水平的研究。具体来说,泪源性EVs可以保护其分子含量,并允许实时监测眼部疾病,如干眼病(DED)、Sjögren病(SJD)、眼部移植物抗宿主病(oGVHD)和糖尿病视网膜病变(DR),这些疾病目前在患者中仍未得到诊断。EVs还提供了作为基因转移载体的潜力,并且间充质干细胞(MSCs)衍生的EVs被证明具有免疫调节作用,显示出对自身免疫性眼病的希望。通过对泪液含量的多组学分析,EVs是一种有前景的眼部疾病生物标志物和治疗药物。
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引用次数: 0
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Ocular Surface
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