Ocular Surface最新文献_第4页

The role of lysophosphatidic acid and its receptors in corneal nerve regeneration 溶血磷脂酸及其受体在角膜神经再生中的作用。

IF 5.9 1区医学 Q1 OPHTHALMOLOGY

Ocular Surface

Pub Date : 2024-12-20 DOI: 10.1016/j.jtos.2024.12.006

Maryam Kheyrollah , Nicola Brandt , Anja U. Bräuer , Stefan Schrader , Sonja Mertsch

The integrity of corneal nerves is critical for ocular surface health, and damages can lead to Neurotrophic Keratopathy (NK). Despite the regenerative abilities of the peripheral nerve system (PNS), corneal nerve regeneration is often incomplete, and the underlying mechanisms are poorly understood. This study aims to identify potential factors that can enhance corneal nerve regeneration for NK treatment, with a focus on Lysophosphatidic acid (LPA).

Thus, the effect of LPA and its underlying pathways in nerve regeneration is investigated in detail using in vitro mouse sensory neurons. To elucidate the impact of LPA as well as to reveal the responsible receptor, several functional assays as well as siRNA-based knock-down experiments were conducted. Additionally, possible changes in underlying pathways were investigated on mRNA levels.

LPA-treated neurons significantly reduced fiber growth. However, LPAR2 knockdown neurons (Lpar2-KD) following LPA treatment showed a significant increase in fiber length. Additionally, LPA-treated neurons demonstrated enhanced levels of Lpar2 mRNA. On the other hand, nerve regeneration indicators such as Ngf, Gap-43, and Cdc42, along with LPA downstream signaling components like Pi3k and Ras, were elevated in Lpar2-KD neurons.

In conclusion, this study elucidates the inhibitory effects of LPA on fiber outgrowth of sensory neurons. Furthermore, LPAR2 was identified as the responsible receptor for the LPA effect. Thus, Lpar2 knockdown might be a promising therapeutic approach to enhance neuronal regeneration in patients with NK.

角膜神经的完整性对眼表健康至关重要，损伤可导致神经营养性角膜病变（NK）。尽管周围神经系统（PNS）具有再生能力，但角膜神经再生通常是不完整的，其潜在机制尚不清楚。本研究旨在确定NK治疗中促进角膜神经再生的潜在因素，重点关注溶血磷脂酸（LPA）。因此，我们利用体外小鼠感觉神经元详细研究了LPA及其潜在通路在神经再生中的作用。为了阐明LPA的影响并揭示负责的受体，进行了几种功能分析以及基于sirna的敲除实验。此外，在mRNA水平上研究潜在通路的可能变化。lpa处理的神经元显著减少纤维生长。然而，LPAR2敲低神经元（LPAR2 - kd）在LPA处理后显示纤维长度显著增加。此外，lpa处理的神经元显示Lpar2 mRNA水平增强。另一方面，神经再生指标如Ngf、Gap-43和Cdc42以及LPA下游信号成分如Pi3k和Ras在Lpar2-KD神经元中升高。综上所述，本研究阐明了LPA对感觉神经元纤维生长的抑制作用。此外，LPAR2被确定为LPA效应的负责受体。因此，Lpar2敲低可能是促进NK患者神经元再生的一种有希望的治疗方法。

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引用次数: 0

Neuropsin, TRPV4 and intracellular calcium mediate intrinsic photosensitivity in corneal epithelial cells 神经蛋白酶、TRPV4 和细胞内钙介导角膜上皮细胞的内在光敏性。

IF 5.9 1区医学 Q1 OPHTHALMOLOGY

Ocular Surface

Pub Date : 2024-12-15 DOI: 10.1016/j.jtos.2024.12.002

Luka Lapajne , Monika Lakk , Christopher N. Rudzitis , Shruti Vemaraju , Richard A. Lang , Marko Hawlina , David Križaj

Purpose

To investigate intrinsic phototransduction in the corneal epithelium and its role in intracellular and inflammatory signaling.

Methods

Optical imaging in isolated corneal epithelial cells (CECs) and debrided epithelia was combined with molecular, biochemical, pharmacological assays and gene deletion studies to track UVB-induced calcium signaling and release of cytokines, chemokines and matrix remodeling enzymes. Results from wild type mouse CECs were compared to data obtained from Opn5^−/− and Trpv4^−/− cells.

Results

UVB stimuli and TRPV4 activity induced epithelial release of IL-1β, IL-17, matrix metalloproteinases MMP-3/MMP-9, and thymic stromal lymphopoietin (TSLP). UVB stimuli evoked [Ca²⁺]_i elevations in dissociated mouse CECs that were partially reduced by inhibition of TRPV4 channels, Trpv4 knockdown and replacement of control saline with Ca²⁺-free saline. UVB-induced Ca²⁺ responses were significantly suppressed by OPN5 deletion and by inhibition of phospholipase C signaling, and responses were abrogated in cells with depleted intracellular Ca²⁺ stores.

Conclusions

Mammalian CECs are intrinsically and constitutively photosensitive. UVB photons are transduced by neuropsin, phospholipase C and CICR signaling, with mouse but not human CE transduction exhibiting a UVB-sensitive TRPV4 component. TRPV4 activity and UVB transduction are linked to cell-autonomous release of proinflammatory, matrix remodeling and nociceptive interleukins and MMPS. TRPV4-induced cytokine release may contribute to the pain induced by mechanical injury of the cornea and CEC photosensing may alert and protect the visual system from ultraviolet B (UVB) radiation -induced snow blindness, injury, vision loss and cancer.

目的：研究角膜上皮细胞的内在光传导及其在细胞内和炎症信号传导中的作用：方法：对分离的角膜上皮细胞（CECs）和剥离的上皮细胞进行光学成像，并结合分子、生化、药理测定和基因缺失研究，以追踪 UVB 诱导的钙信号转导以及细胞因子、趋化因子和基质重塑酶的释放。野生型小鼠 CECs 的结果与 Opn5-/- 和 Trpv4-/- 细胞的数据进行了比较：结果：UVB 刺激和 TRPV4 活性诱导上皮细胞释放 IL-1β、IL-17、基质金属蛋白酶 MMP-3/MMP-9 和胸腺基质淋巴细胞生成素 (TSLP)。抑制 TRPV4 通道、敲除 Trpv4 和用不含 Ca2+ 的生理盐水替代对照组生理盐水可部分降低 UVB 刺激在离体小鼠 CECs 中引起的[Ca2+]i 升高。通过删除 OPN5 和抑制磷脂酶 C 信号传导，UVB 诱导的 Ca2+ 反应被显著抑制，而在细胞内 Ca2+ 储存耗尽的细胞中，反应也会减弱：结论：哺乳动物 CECs 具有内在的组成型光敏性。UVB光子通过神经蛋白酶、磷脂酶C和CICR信号传导，小鼠而非人的CE传导表现出UVB敏感的TRPV4成分。TRPV4 活性和 UVB 转导与细胞自主释放促炎、基质重塑和痛觉白细胞介素和 MMPS 有关。TRPV4 诱导的细胞因子释放可能是角膜机械损伤引起疼痛的原因之一。CEC 光传感可提醒和保护视觉系统免受紫外线 B（UVB）辐射引起的雪盲、损伤、视力丧失和癌症。

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引用次数: 0

Efficacy and safety of AZR-MD-001 selenium sulfide ophthalmic ointment in adults with meibomian gland dysfunction over six months of treatment: A Phase 2, vehicle-controlled, randomized extension trial AZR-MD-001硫化硒眼药膏治疗6个月成人睑板腺功能障碍的疗效和安全性：一项2期、载体对照、随机扩展试验

IF 5.9 1区医学 Q1 OPHTHALMOLOGY

Ocular Surface

Pub Date : 2024-11-28 DOI: 10.1016/j.jtos.2024.11.008

Laura E. Downie , Jennifer P. Craig , Fiona Stapleton , Jacqueline Tan , Lyndon W. Jones , Alison Ng , Mark Hinds , Charles Bosworth , Yair Alster

Purpose

To determine the efficacy and safety of AZR-MD-001 (0.5 % and 1.0 %) ophthalmic ointment, relative to vehicle, over 3–6 months of treatment, in participants with meibomian gland dysfunction (MGD).

Methods

This was a Phase 2, randomized, vehicle-controlled, multicenter extension clinical trial. Eligible participants were adults with MGD (meibomian gland secretion score (MGS) ≤12 out of 15 glands) who discontinued all other dry eye or MGD treatments. Participants were randomized 1:1:1 to apply AZR-MD-001 1.0 %, 0.5 %, or vehicle to the lower eyelids, twice weekly. Key exploratory endpoints included the least-squared mean difference between groups in the change from baseline in clinical signs (meibomian gland yielding score; MGYLS) and symptoms (Ocular Surface Disease Index; OSDI), at clinic visits at Month 4.5 and 6, and safety measures from 36 months.

Results

Participants (66.5 % female) were randomized, at baseline, to AZR-MD-001 0.5 % (n = 82), 1.0 % (n = 83), or vehicle (n = 80). Statistically significant improvements, compared to vehicle, were observed at Month 6 in MGYLS for both AZR-MD-001 groups (0.5 % group: 1.9, 95 % CI 0.9 to 2.8, P = 0.002; 1.0 % group: 1.1, 95 % CI 0.2 to 2.1, P = 0.026), and in OSDI score for the 0.5 % group (−4.5, 95 % CI -8.0 to −0.9, P = 0.0135). The most common adverse events for AZR-MD-001 were application site pain, superficial punctate keratitis and eye pain; most were mild to moderate in severity, and decreased in incidence over time.

Conclusions

AZR-MD-001 (0.5 %) was efficacious in treating signs and symptoms of MGD over six months, with a lower observed incidence of new adverse events over time.

目的：确定AZR-MD-001（0.5%和1.0%）眼药膏相对于对照物治疗3-6个月对睑板腺功能障碍（MGD）患者的疗效和安全性。方法：这是一项2期、随机、载体对照、多中心扩展临床试验。符合条件的参与者是患有MGD（睑板腺分泌评分(MGS)≤15个腺体中的12个）的成年人，他们停止了所有其他干眼或MGD治疗。参与者按1:1:1随机分组，每周两次将AZR-MD-001 1.0%、0.5%或载体涂抹在下眼睑。关键的探索性终点包括两组临床体征从基线变化的最小平方平均差异(睑板腺生成评分；MGYLS)和症状(眼表疾病指数；OSDI)，在第4.5个月和第6个月的门诊就诊，以及3-6个月的安全措施。结果：参与者（66.5%女性）在基线时随机分为AZR-MD-001 0.5% （n=82）、1.0% （n=83）或对照（n=80）组。与对照组相比，AZR-MD-001组在第6个月MGYLS的改善具有统计学意义(0.5%组：1.9,95% CI 0.9 ~ 2.8， P=0.002；1.0%组：1.1,95% CI 0.2 ~ 2.1， P=0.026)， 0.5%组OSDI评分为-4.5,95% CI -8.0 ~ -0.9， P=0.0135)。AZR-MD-001最常见的不良事件是应用部位疼痛、浅表点状角膜炎和眼睛疼痛；大多数是轻度到中度的严重程度，发病率随着时间的推移而下降。结论：AZR-MD-001（0.5%）在治疗MGD的体征和症状6个月内有效，随着时间的推移，观察到的新不良事件发生率较低。

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引用次数: 0

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