Ocular Surface最新文献_第5页

Ocular surface squamous neoplasia: Update on genetics, epigenetics and opportunities for targeted therapy 眼表鳞状瘤变：遗传学、表观遗传学和靶向治疗的最新进展

IF 5.9 1区医学 Q1 OPHTHALMOLOGY

Ocular Surface

Pub Date : 2024-11-26 DOI: 10.1016/j.jtos.2024.11.006

Nefeli Eleni Kounatidou , Evangelos Vitkos , Sotiria Palioura

Purpose

The purpose of this review is to explore the molecular foundations of ocular surface squamous neoplasia (OSSN), focusing on the genetic and epigenetic aspects. While current management strategies include surgical excision and medical therapies, the understanding of OSSN's molecular basis remains limited, hindering the development of targeted treatments.

Methods

A comprehensive MEDLINE search was conducted for literature published between January 1993 and October 2023. Only studies with original data on molecular, genetic, or epigenetic mechanisms, such as mutations, gene expression, and genetic predispositions were included. Articles were excluded if they focused solely on clinical management without addressing these factors, or if they were reviews, editorials, or opinion pieces.

Results

The search yielded a total of 108 articles, out of which 39 articles met the criteria for further analysis. Investigations into OSSN have identified key DNA mutations in the TP53, HGF, EGFR, TERT, and CDKN2A genes, indicating common oncogenic pathways shared with other squamous cell carcinomas (SCCs). Significant epigenetic changes were identified, including DNA methylation, histone modifications, and altered miRNA expression patterns. Epigenetic dysregulation of critical tumor suppressors and oncoproteins, further highlight the complex genetic landscape of OSSN.

Conclusion

The molecular alterations identified in OSSN not only enhance our understanding of its biology but also have potential as novel biomarkers for early detection, prognostic evaluation, and as therapeutic targets. The identification of genetic and epigenetic markers in OSSN signifies progress towards personalized medicine approaches. Further studies and collaborative efforts are essential to validate these molecular markers and translate them into clinical practice, potentially revolutionizing OSSN management and improving patient outcomes.

目的探讨眼表鳞状瘤变（OSSN）的分子基础，重点从遗传学和表观遗传学方面进行探讨。虽然目前的治疗策略包括手术切除和药物治疗，但对OSSN分子基础的了解仍然有限，阻碍了靶向治疗的发展。方法对1993年1月~ 2023年10月发表的文献进行综合MEDLINE检索。仅包括具有分子、遗传或表观遗传机制（如突变、基因表达和遗传易感性）原始数据的研究。如果文章只关注临床管理而不考虑这些因素，或者是评论、社论或观点文章，则排除。结果共检索到108篇文献，其中39篇符合进一步分析的标准。对OSSN的研究已经发现了TP53、HGF、EGFR、TERT和CDKN2A基因中的关键DNA突变，表明与其他鳞状细胞癌（SCCs）共有的共同致癌途径。发现了显著的表观遗传变化，包括DNA甲基化、组蛋白修饰和miRNA表达模式的改变。关键肿瘤抑制因子和癌蛋白的表观遗传失调，进一步凸显了OSSN的复杂遗传格局。结论在OSSN中发现的分子改变不仅增强了我们对其生物学的理解，而且具有作为早期检测、预后评估和治疗靶点的新生物标志物的潜力。OSSN中遗传和表观遗传标记的识别标志着个性化医疗方法的进步。进一步的研究和合作对于验证这些分子标记并将其转化为临床实践至关重要，这可能会彻底改变OSSN的管理并改善患者的预后。

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引用次数: 0

Diagnostic performance and optimal cut-off values for tear film lipid layer grading and thickness in dry eye disease: An investigator-masked, randomised crossover study 干眼症泪膜脂质层分级和厚度的诊断性能和最佳临界值：一项研究者掩蔽的随机交叉研究。

IF 5.9 1区医学 Q1 OPHTHALMOLOGY

Ocular Surface

Pub Date : 2024-10-01 DOI: 10.1016/j.jtos.2024.09.004

Michael T.M. Wang, Barry Power, Ally L. Xue, Jennifer P. Craig

引用次数: 0

Cell death pathways in dry eye disease: Insights into ocular surface inflammation 干眼症中的细胞死亡途径：洞察眼表炎症。

IF 5.9 1区医学 Q1 OPHTHALMOLOGY

Ocular Surface

Pub Date : 2024-10-01 DOI: 10.1016/j.jtos.2024.11.004

Jiani Li , Xiaorui Bao , Shujia Guo , Yuhan Huang , Caihong Huang , Jiaoyue Hu , Zuguo Liu

Dry eye disease (DED) is increasingly prevalent, with inflammation playing a crucial role in its pathogenesis. Severe cases of DED result in significant ocular discomfort and visual impairment due to damage and loss of ocular surface epithelial cells. The precise mechanisms underlying the loss of these epithelial cells remain a subject of ongoing research and debate. Programmed cell death (PCD) mechanisms, including pyroptosis, apoptosis, and necroptosis, are known to be critical in maintaining ocular surface homeostasis and responding to stressors in DED. The concept of PANoptosis, which integrates elements of various PCD pathways, has been implicated in the development of numerous systemic diseases, including infections, cancer, neurodegenerative, and inflammatory conditions. It also provides novel insights into the inflammatory processes underlying DED. This review highlights the crosstalk of PCD pathways in DED, particularly the significance of PANoptosis in ocular inflammation and its potential as a therapeutic target for more effective interventions.

干眼症（DED）的发病率越来越高，炎症在其发病机制中起着至关重要的作用。由于眼表上皮细胞受损和丧失，严重的干眼症患者会出现明显的眼部不适和视力损害。这些上皮细胞丧失的确切机制仍是一个持续研究和争论的主题。众所周知，程序性细胞死亡（PCD）机制，包括热凋亡、细胞凋亡和坏死，在维持眼表平衡和应对 DED 中的应激源方面至关重要。整合了各种 PCD 途径要素的泛凋亡（PANoptosis）概念已被认为与多种全身性疾病（包括感染、癌症、神经退行性疾病和炎症）的发展有关。这也为了解 DED 的炎症过程提供了新的视角。本综述强调了 DED 中 PCD 通路的相互影响，特别是 PANoptosis 在眼部炎症中的重要性及其作为更有效干预的治疗靶点的潜力。

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引用次数: 0

Metabolomics of basal tears in amyotrophic lateral sclerosis: A cross-sectional study 肌萎缩侧索硬化症患者基底泪液的代谢组学：一项横断面研究。

IF 5.9 1区医学 Q1 OPHTHALMOLOGY

Ocular Surface

Pub Date : 2024-10-01 DOI: 10.1016/j.jtos.2024.09.005

Raoul K. Khanna , Sophie Catanese , Geoffroy Mortemousque , Camille Dupuy , Antoine Lefevre , Patrick Emond , Stéphane Beltran , Valérie Gissot , Pierre-Jean Pisella , Hélène Blasco , Philippe Corcia

Purpose

Amyotrophic lateral sclerosis (ALS) clinical variability, along with the lack of conclusive diagnostic instruments, result in average diagnosis delays of 9 months. This study aimed to assess whether metabolomic profiling of basal tears in ALS patients could act as a biological marker for diagnosing ALS, predicting prognosis, and discriminating between endophenotypes.

Methods

A single-center prospective case-control study was conducted in France from September 2021 to March 2023 including patients with ALS according to the revised EI Escorial criteria. Two microliters of basal tears were collected using microcapillary glass tubes and analyzed with ultra-high performance liquid chromatography coupled with mass spectrometry. Both univariate and multivariate analyses were performed.

Results

Twenty-five patients with ALS and 30 controls were included. No significant differences in metabolite levels were found between ALS and control groups (p > 0.05). The basal tear metabolome significantly discriminated bulbar and spinal forms of ALS based on 6 metabolites, among which 5 were decreased (aniline, trigonelline, caffeine, theophylline and methyl beta-D-galactoside) in the bulbar form and 1 was decreased in the spinal form (dodecanedioic acid).

Conclusion

This study represents the first prospective analysis of basal tear metabolomics in individuals with ALS. Despite the inability to distinguish between ALS patients and controls based on metabolic signatures, these findings could contribute to understanding the phenotypic diversity of ALS. Notably, distinct metabolic profiles were identified that differentiate between the bulbar and spinal forms of the disease.

目的：肌萎缩性脊髓侧索硬化症（ALS）临床表现多变，加上缺乏确凿的诊断工具，导致平均诊断延迟9个月。本研究旨在评估 ALS 患者基底泪液的代谢组学分析是否可作为诊断 ALS、预测预后和区分内分型的生物标记物：方法：2021 年 9 月至 2023 年 3 月在法国开展了一项单中心前瞻性病例对照研究，根据修订后的 EI Escorial 标准纳入 ALS 患者。研究人员使用微毛细管玻璃管收集了两微升的基础泪液，并使用超高效液相色谱法和质谱法进行了分析。进行了单变量和多变量分析：结果：共纳入 25 名 ALS 患者和 30 名对照组。ALS 组和对照组的代谢物水平无明显差异（P>0.05）。基础泪液代谢组中的 6 种代谢物可明显区分脊髓侧索硬化症的球部和脊柱型，其中球部型患者的 5 种代谢物（苯胺、三尖杉碱、咖啡因、茶碱和甲基 beta-D-半乳糖苷）含量降低，脊柱型患者的 1 种代谢物（十二碳二酸）含量降低：这项研究首次对 ALS 患者的基础泪液代谢组学进行了前瞻性分析。尽管无法根据代谢特征区分 ALS 患者和对照组，但这些发现有助于了解 ALS 的表型多样性。值得注意的是，研究还发现了区分脊髓侧索硬化症和球部侧索硬化症的不同代谢特征。

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引用次数: 0

A tribute to Dr. Alison McDermott and her contributions to the ocular surface 向艾莉森-麦克德莫特博士及其对眼表的贡献致敬。

IF 5.9 1区医学 Q1 OPHTHALMOLOGY

Ocular Surface

Pub Date : 2024-10-01 DOI: 10.1016/j.jtos.2024.10.008

Rachel Redfern OD, PhD , Srihari Narayanan OD, PhD , Suzanne Fleiszig OD, PhD , Eric Pearlman PhD

引用次数: 0

Preventing and treating neurotrophic keratopathy by a single intrastromal injection of AAV-mediated gene therapy 通过一次性腹腔注射 AAV 介导的基因疗法预防和治疗神经营养性角膜病。

IF 5.9 1区医学 Q1 OPHTHALMOLOGY

Ocular Surface

Pub Date : 2024-10-01 DOI: 10.1016/j.jtos.2024.09.010

Lin Cong , Benxiang Qi , Wenhui Ma , Zhongmei Ren , Qian Liang , Qingjun Zhou , Bi Ning Zhang , Lixin Xie

Purpose

Neurotrophic keratopathy (NK) is a degenerative corneal condition resulting from corneal nerve injury. Current therapies, including the recombinant human nerve growth factor (rhNGF) therapy, requires continuous administration. This study aims to develop a novel and highly effective gene therapy strategy for the prevention and treatment of NK.

Methods

Adeno-associated virus (AAV) was transduced into corneal stromal cells by intrastromal injection. Three dimensional corneal wholemount imaging with co-immunostaining of ZO-1 and tubulin was utilized to assess the transduction of AAV.rh10. The efficacy of prevention and treatment of NK by a single intrastromal injection of AAV-Ngf was tested using capsaicin mouse model, herpes simplex keratitis (HSK) model, type Ⅱ diabetes model and alkali burn model. rhNGF eye drops served as the positive control.

Results

Intrastromal injection of AAV.rh10 efficiently transduced the subepithelial nerve plexus and retrogradely transported to the trigeminal ganglion (TG). A single injection of AAV.rh10-Ngf can significantly promote corneal nerve repair, accelerate corneal epithelial repair, reduce corneal stromal edema, and improve corneal sensitivity across the four NK models. The therapeutic effects were consistent with those achieved by continuous administration of rhNGF drops by 6 times daily.

Conclusions

This proof-of-concept study demonstrates that AAV.rh10-Ngf gene therapy is a promising method for preventing and treating of NK. Our results underline the potential for developing clinical trials to further explore the safety and efficacy of such gene therapy.

目的：神经营养性角膜病（NK）是一种由角膜神经损伤引起的角膜退行性病变。目前的疗法，包括重组人神经生长因子（rhNGF）疗法，需要持续给药。本研究旨在开发一种预防和治疗 NK 的新型高效基因治疗策略：方法：通过基质内注射将腺相关病毒（AAV）转入角膜基质细胞。方法：将腺相关病毒（AAV）通过基质内注射转导到角膜基质细胞中，利用三维角膜全层成像和 ZO-1 与微管蛋白的联合免疫染色来评估 AAV.rh10 的转导情况。在辣椒素小鼠模型、单纯疱疹性角膜炎（HSK）模型、Ⅱ型糖尿病模型和碱烧伤模型中测试了一次性鞘内注射 AAV-Ngf 预防和治疗 NK 的疗效，rhNGF 滴眼液作为阳性对照：结果：AAV.rh10的鞘内注射能有效转导上皮下神经丛，并逆行转运至三叉神经节（TG）。在四种 NK 模型中，单次注射 AAV.rh10-Ngf 可显著促进角膜神经修复、加速角膜上皮修复、减轻角膜基质水肿并提高角膜敏感性。这些治疗效果与每日6次持续滴注rhNGF所取得的效果一致：这项概念验证研究表明，AAV.rh10-Ngf 基因疗法是一种预防和治疗 NK 的有效方法。我们的研究结果凸显了开展临床试验以进一步探索此类基因疗法的安全性和有效性的潜力。

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引用次数: 0

Target specification and therapeutic potential of extracellular vesicles for regulating corneal angiogenesis, lymphangiogenesis, and nerve repair 细胞外囊泡在调节角膜血管生成、淋巴管生成和神经修复方面的靶标定位和治疗潜力。

IF 5.9 1区医学 Q1 OPHTHALMOLOGY

Ocular Surface

Pub Date : 2024-10-01 DOI: 10.1016/j.jtos.2024.10.005

Cameron Pedersen , Victoria T. Chen , Paula Herbst , Runze Zhang , Amr Elfert , Abhi Krishan , Dimitri T. Azar , Jin-Hong Chang , Wen-Yang Hu , Tobias P. Kremsmayer , Elmira Jalilian , Ali R. Djalilian , Victor H. Guaiquil , Mark I. Rosenblatt

Extracellular vesicles, including exosomes, are small extracellular vesicles that range in size from 30 nm to 10 μm in diameter and have specific membrane markers. They are naturally secreted and are present in various bodily fluids, including blood, urine, and saliva, and through the variety of their internal cargo, they contribute to both normal physiological and pathological processes. These processes include immune modulation, neuronal synapse formation, cell differentiation, cancer metastasis, angiogenesis, lymphangiogenesis, progression of infectious disease, and neurodegenerative disorders like Alzheimer's and Parkinson's disease. In recent years, interest has grown in the use of exosomes as a potential drug delivery system for various diseases and injuries. Importantly, exosomes originating from a patient's own cells exhibit minimal immunogenicity and possess remarkable stability along with inherent and adjustable targeting capabilities. This review explores the roles of exosomes in angiogenesis, lymphangiogenesis, and nerve repair with a specific emphasis on these processes within the cornea. Furthermore, it examines exosomes derived from specific cell types, discusses the advantages of exosome-based therapies in modulating these processes, and presents some of the most established methods for exosome isolation. Exosome-based treatments are emerging as potential minimally invasive and non-immunogenic therapies that modulate corneal angiogenesis and lymphangiogenesis, as well as enhance and accelerate endogenous corneal nerve repair.

细胞外囊泡，包括外泌体，是一种小的细胞外囊泡，直径从 30 纳米到 10 微米不等，具有特定的膜标记。它们是自然分泌的，存在于血液、尿液和唾液等各种体液中，通过其内部货物的多样性，它们对正常的生理和病理过程都有贡献。这些过程包括免疫调节、神经元突触形成、细胞分化、癌症转移、血管生成、淋巴管生成、传染病进展以及阿尔茨海默氏症和帕金森氏症等神经退行性疾病。近年来，人们对外泌体作为一种潜在的药物输送系统用于治疗各种疾病和损伤的兴趣与日俱增。重要的是，源于患者自身细胞的外泌体具有极低的免疫原性、出色的稳定性以及固有的可调节靶向能力。本综述探讨了外泌体在血管生成、淋巴管生成和神经修复中的作用，并特别强调了角膜中的这些过程。此外，它还研究了从特定细胞类型中提取的外泌体，讨论了基于外泌体的疗法在调节这些过程中的优势，并介绍了一些最成熟的外泌体分离方法。基于外泌体的疗法正在成为潜在的微创、非免疫原性疗法，可调节角膜血管生成和淋巴管生成，并增强和加速内源性角膜神经修复。

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引用次数: 0

Simple limbal epithelial transplantation versus cultivated limbal epithelial transplantation in ocular burns 眼烧伤中的单纯角膜缘上皮移植与角膜缘上皮培养移植。

IF 5.9 1区医学 Q1 OPHTHALMOLOGY

Ocular Surface

Pub Date : 2024-10-01 DOI: 10.1016/j.jtos.2024.10.007

Namrata Sharma , Renu Venugopal , Sujata Mohanty , K. Priyadarshini , Ritu Nagpal , Deepali Singhal , Aafreen Bari , Tanuj Dada , Prafulla Kumar Maharana , Tushar Agarwal , Ashish Dutt Upadhyay

Purpose

To compare the outcomes of simple limbal epithelial transplantation (SLET) with cultivated limbal epithelial transplantation (CLET) for the management of total limbal stem cell deficiency (LSCD) in eyes with unilateral ocular burns.

Design

Randomized controlled trial.

Methods

100 patients (100 eyes) with unilateral total LSCD following ocular burns undergoing autologous Limbal Stem Cell Transplantation (LSCT) were enrolled and randomized into SLET and CLET groups. Restoration of an epithelized ocular surface was the primary outcome measure. Occurrences of progressive conjunctivalization and persistent epithelial defects postoperatively were considered surgical failures.

Results

Mean age was 20.2 ± 13.1 years (SLET) and 22.6 ± 14.3 years (CLET) (p = 0.363). Alkali burn was the most common causative factor in both groups and had comparable mean logMAR BCVA at presentation [SLET: 2.33 ± 0.5, CLET: 2.23 ± 1.48 (p = 0.652)]. Median time interval between injury and surgical intervention was 18 months (SLET) and 12 months (CLET) (p = 0.06). 88 % eyes in SLET group maintained a stable ocular surface at 1 year period versus CLET group (86 %) (p = 0.999). Mean logMAR BCVA significantly improved in both groups with SLET having significantly better BCVA versus CLET at 6 months (p = 0.0390), 1 year (p = 0.0001), 2 year (p = 0.0001) and 3 years (p = 0.0001) follow up. Kaplan-Meier survival analysis was statistically insignificant amongst the 2 groups (p = 0.590).

Conclusions

Compared to CLET, SLET is equally efficacious in restoring and maintaining a stable ocular surface in eyes with total LSCD due to ocular burns, with the added advantage of providing superior visual outcomes.

目的：比较单纯瓣上皮移植术（SLET）和培养瓣上皮移植术（CLET）治疗单侧眼烧伤后全瓣干细胞缺乏症（LSCD）的疗效：随机对照试验。方法：100 名眼部烧伤后单侧全缘干细胞缺乏症患者（100 只眼）接受自体眼缘干细胞移植术（LSCT），并随机分为 SLET 组和 CLET 组。恢复上皮化的眼表是衡量疗效的主要指标。术后出现进行性结膜化和持续性上皮缺损被视为手术失败：平均年龄为 20.2 ± 13.1 岁（SLET）和 22.6 ± 14.3 岁（CLET）（p = 0.363）。碱烧伤是两组患者最常见的致病因素，两组患者发病时的 BCVA 平均对数值相当[SLET：2.33 ± 0.5，CLET：2.23 ± 1.48 (p = 0.652)]。从受伤到手术干预的中位时间间隔为 18 个月（SLET）和 12 个月（CLET）（p = 0.06）。SLET组88%的眼睛在1年后眼表保持稳定，而CLET组为86%（p = 0.999）。两组患者的 BCVA 平均对数均有显著改善，SLET 组在 6 个月（p = 0.0390）、1 年（p = 0.0001）、2 年（p = 0.0001）和 3 年（p = 0.0001）随访期间的 BCVA 均明显优于 CLET 组。Kaplan-Meier生存率分析结果显示，两组间差异无统计学意义（p = 0.590）：结论：与 CLET 相比，SLET 在恢复和维持因眼部烧伤导致的全 LSCD 眼的眼表稳定方面同样有效，而且还具有视觉效果更佳的优势。

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引用次数: 0

Readership awareness series – paper 14: The submission Dilemma - How to choose a journal? 读者意识丛书--论文 14：投稿困境--如何选择期刊？

IF 5.9 1区医学 Q1 OPHTHALMOLOGY

Ocular Surface

Pub Date : 2024-10-01 DOI: 10.1016/j.jtos.2024.11.003

Mohammad Javed Ali, Ali Djalilian

引用次数: 0

Cytarabine chemotherapy induces meibomian gland dysfunction 阿糖胞苷化疗诱发睑板腺功能障碍

IF 5.9 1区医学 Q1 OPHTHALMOLOGY

Ocular Surface

Pub Date : 2024-10-01 DOI: 10.1016/j.jtos.2024.10.002

Ren Liu , Jianwen Xue , Jiaxu Han, Mengqian Tu, Wenhui Wang, Ziyan Chen, Xiaobing Qian, Bing Xiao, Lingyi Liang

Purpose

Cytarabine (Ara-C) chemotherapy causes symptoms resembling meibomian gland dysfunction (MGD), suggesting potential associations between Ara-C and MGD. In this study, the pathological effects of Ara-C on MGD were investigated in a rodent model.

Methods

Mice received Ara-C with or without rosiglitazone (PPARγ agonist) for 7 consecutive days. Slit-lamp biomicroscope was used for ocular examinations. Immunofluorescence detected acinar cell proliferation, differentiation, and ductal keratinization in the meibomian gland (MG). Lipid accumulation was evaluated by Oil Red O and LipidTox staining. Lipogenic status, FoxO1/FoxO3a cellular localization, and oxidative stress were visualized via immunohistochemistry. Western blotting assessed relative protein expression and AKT/FoxO1/FoxO3a pathway phosphorylation.

Results

Ara-C (50 mg/kg) did not affect mouse survival but induced damage to ocular surface microenvironment, including corneal epithelial defects, MG orifice plugging and acinar dropout, and lacrimal gland (LG) dysfunction. Ara-C intervention inhibited proliferation and caused progenitor loss in the MG, as evidenced by reduced PCNA + labeling and P63+/Lrig1+ basal cell numbers. The MG ducts of Ara-C-treated mice exhibited marked dilatation, lipid deposition, and hyperkeratinization (K1/K10 overexpression). Ara-C disrupted MG lipid metabolism by downregulating PPARγ and its downstream lipogenic targets AWAT2/SOAT1/ELOVL4 and upregulating HMGCR. Dephosphorylation of AKT and the subsequent nuclear translocation of FoxO1/FoxO3a contributed to Ara-C-induced PPARγ downregulation. Ara-C triggered oxidative stress with increases in 4-HNE and 8-OHdG and Keap1/Nrf2/HO-1/SOD1 axis dysregulation. Rosiglitazone treatment ameliorated MGD-associated pathological manifestations, LG function, MG lipid metabolism, and oxidative stress in Ara-C-exposed mice.

Conclusions

Systemic Ara-C chemotherapy exerted topical cytotoxic effects on the ocular surface, and PPARγ restoration by rosiglitazone mitigated Ara-C-induced MGD alterations.

目的阿糖胞苷（Ara-C）化疗会导致类似睑板腺功能障碍（MGD）的症状，这表明 Ara-C 和 MGD 之间可能存在关联。本研究在啮齿动物模型中研究了 Ara-C 对 MGD 的病理影响。使用裂隙灯生物显微镜进行眼部检查。免疫荧光检测睑板腺（MG）中的尖状细胞增殖、分化和导管角化。油红 O 和脂毒染色法评估了脂质积累情况。通过免疫组化观察生脂状态、FoxO1/FoxO3a细胞定位和氧化应激。结果 Ara-C（50 毫克/千克）不影响小鼠的存活率，但会导致眼表微环境受损，包括角膜上皮缺损、MG 口堵塞和尖锐湿疣脱落以及泪腺（LG）功能障碍。Ara-C干预抑制了MG的增殖并导致祖细胞丢失，PCNA+标记和P63+/Lrig1+基底细胞数量的减少证明了这一点。经 Ara-C 处理的小鼠的 MG 管表现出明显的扩张、脂质沉积和过度角质化（K1/K10 过度表达）。Ara-C 通过下调 PPARγ 及其下游致脂靶标 AWAT2/SOAT1/ELOVL4 和上调 HMGCR 破坏了 MG 的脂质代谢。AKT 的去磷酸化和随后 FoxO1/FoxO3a 的核转位有助于 Ara-C 诱导的 PPARγ 下调。Ara-C 引发氧化应激，导致 4-HNE 和 8-OHdG 增加，Keap1/Nrf2/HO-1/SOD1 轴失调。结论系统性 Ara-C 化疗对眼表产生局部细胞毒性作用，罗格列酮对 PPARγ 的恢复减轻了 Ara-C 诱导的 MGD 改变。

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引用次数: 0