Corneal Neovascularization

角膜新生血管形成
  • 文章类型: Journal Article
    角膜新生血管形成(CoNV)是全球视力障碍的第二大常见原因,是眼外伤引起的致盲病理改变,感染,和其他因素。CoNV的治疗有一些局限性,因此,研究新的治疗靶点至关重要。角膜上皮屏障,这是眼表的初始屏障,是保护眼睛免受内部环境变化或外部环境入侵的重要结构。本研究旨在整理有关角膜上皮屏障损伤对血管内皮细胞(VECs)活化的调节作用的证据。基底膜(BM)降解,分化,迁移,和VEC的扩散,血管成熟和稳定性,以及CoNV的其他关键流程,从而为CoNV靶向角膜上皮屏障修复治疗提供新的思路。
    Corneal neovascularization (CoNV) is the second leading common cause of vision impairment worldwide and is a blinding pathological alteration brought on by ocular trauma, infection, and other factors. There are some limitations in the treatment of CoNV, hence it\'s critical to look into novel therapeutic targets. The corneal epithelial barrier, which is the initial barrier of the ocular surface, is an important structure that shields the eye from changes in the internal environment or invasion by the external environment. This study sought to collate evidence on the regulation of corneal epithelial barrier injury on the activation of vascular endothelial cells (VECs), basement membrane (BM) degradation, differentiation, migration, and proliferation of VECs, vascular maturation and stability, and other key processes in CoNV, so as to provide a novel concept for CoNV therapy targeting corneal epithelial barrier repair.
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  • 文章类型: Journal Article
    背景/目的:无虹膜相关角膜病变(AAK)是先天性无虹膜的潜在视力威胁病理,其潜在的病因和有效的治疗仍不清楚。方法:进行这项前瞻性研究,以评估和比较单独或联合羊膜移植(AMT)进行浅表角膜切除术(SK)后的短期结果。这里,在76例4级AAK患者中纳入76只眼。在所有的眼睛,为了在术前评估角膜缘上皮干细胞(LESC)的效率,建立了共聚焦显微镜中角膜上皮细胞的存在。分析包括:最佳矫正视力(BCVA),AAK分期和参与角膜新生血管(CNV)的角膜象限数量。结果:术后6个月,两组的平均BCVA为0.05,范围为0.002~0.1.当*单独使用SK*时,94.29%的患者出现BCVA改善,与AMT联合使用时,为92.68%。根据手术类型的不同,治疗效果没有统计学上的显着差异,关于BCVA,AAK的阶段和具有CNV的象限数。结论:对于与LESC部分效率相关的晚期AAK,仅SK是一种有效的短期结局,限于六个月。
    Background/Objectives: Aniridia-associated keratopathy (AAK) is a potentially vision-threatening pathology in congenital aniridia, for which both the underlying etiopathogenesis and effective treatment remain unclear. Methods:This prospective study was conducted to assess and compare the short-term outcome after superficial keratectomy (SK) alone or in a combination with an amniotic membrane transplantation (AMT). Here, 76 eyes were enrolled in 76 patients with grade 4 AAK. In all eyes, in order to assess preoperatively the efficiency of the limbal epithelial stem cells (LESC), the presence of corneal epithelial cells in confocal microscopy was established. The analyses included: best corrected visual acuity (BCVA), the stage of AAK and the number of corneal quadrants involved in corneal neovascularization (CNV). Results: Six months after surgery, the mean BCVA was 0.05 and ranged from 0.002 up to 0.1 in both groups. Improvement in BCVA occurred in 94.29% patients when *SK alone* was performed, and in 92.68% when in combination with AMT. There were no statistically significant differences in the effect of therapy depending on the type of surgery, regarding BCVA, stage of AAK and the number of quadrants with CNV. Conclusions: SK alone is an effective procedure in short outcomes limited to six months for advanced AAK in association with LESC partial efficiency.
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  • 文章类型: Journal Article
    背景:目前,对于新生血管和淋巴管生成没有完美的治疗方法,每种治疗方法都有其并发症和副作用。本研究旨在探讨大麻二酚的抗血管生成和抗炎作用及其作用机制。
    方法:采用缝合法建立体内角膜新生血管(CNV)模型,研究CBD对缝合诱导的角膜炎症的抑制作用,病理性血管形成,和淋巴管生成。此外,研究了CBD对免疫细胞的影响。体外方法学,包括细胞分选和共培养,被用来阐明其作用机制。
    结果:与CNV组相比,CBD可以抑制CNV,淋巴管生成,和通过缝合方法诱导的炎症。此外,CBD特异性诱导CD45+CD11b+Gr-1+细胞上调,显着抑制体外CD4+T淋巴细胞的增殖,表现为CD31+表型,证明它们是骨髓来源的抑制细胞(MDSCs)。我们向小鼠施用抗Gr-1以在体内消除MDSCs,并发现抗Gr-1部分逆转了CBD的抗炎和血管生成作用。此外,我们发现,与正常组的MDSCs相比,CBD诱导的MDSCs过表达过氧化物酶体增殖物激活受体γ(PPAR-γ)。在小鼠中施用PPAR-γ抑制剂几乎逆转了CBD对MDSCs的诱导,证明PPAR-γ在CBD功能中的作用。
    结论:这项研究表明,CBD可能通过激活核受体PPAR-γ诱导MDSCs上调,发挥抗炎作用,抗血管生成,和淋巴管生成作用,揭示角膜新生血管和淋巴管生成的潜在治疗靶点。
    BACKGROUND: Currently, no perfect treatment for neovascularization and lymphangiogenesis exist, and each treatment method has its complications and side effects. This study aimed to investigate the anti-angiogenic and anti-inflammatory effects of cannabidiol and its mechanism of action.
    METHODS: An in vivo corneal neovascularization (CNV) model was established using the suture method to investigate the inhibitory effects of CBD on suture-induced corneal inflammation, pathological blood vessel formation, and lymphangiogenesis. Additionally, the impact of CBD on immune cells was studied. In vitro methodologies, including cell sorting and co-culture, were employed to elucidate its mechanism of action.
    RESULTS: Compared with the CNV group, CBD can inhibit CNV, lymphangiogenesis, and inflammation induced via the suture method. In addition, CBD specifically induced CD45+CD11b+Gr-1+ cell upregulation, which significantly inhibited the proliferation of CD4+ T lymphocytes in vitro and exhibited a CD31+ phenotype, proving that they were myeloid-derived suppressor cells (MDSCs). We administered anti-Gr-1 to mice to eliminate MDSCs in vivo and found that anti-Gr-1 partially reversed the anti-inflammatory and angiogenic effects of CBD. Furthermore, we found that compared with MDSCs in the normal group, CBD-induced MDSCs overexpress peroxisome proliferator-activated receptor-gamma (PPAR-γ). Administering PPAR-γ inhibitor in mice almost reversed the induction of MDSCs by CBD, demonstrating the role of PPAR-γ in the function of CBD.
    CONCLUSIONS: This study indicates that CBD may induce MDSCs upregulation by activating the nuclear receptor PPAR-γ, exerting anti-inflammatory, antiangiogenic, and lymphangiogenic effects, and revealing potential therapeutic targets for corneal neovascularization and lymphangiogenesis.
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  • 文章类型: Journal Article
    报告2例伴有化脓性汗腺炎(HS)的双侧眼睑结膜炎。
    病例报告和文献复习。2例HS患者的临床病程,包括眼部表现和医疗管理,被描述。
    两名年龄分别为18岁和23岁的重度HS的女性患者表现为双侧睑角膜结膜炎。共有裂隙灯的发现包括双侧角膜新生血管形成和下角膜变薄。在第一种情况下需要系统性免疫抑制,这导致了患者的眼科和皮肤病学检查结果的改善。
    我们报告了2例严重HS患者的双侧眼睑结膜炎。据我们所知,这种关联以前没有在文献中描述过.鉴于其潜在的视觉破坏性表现以及早期治疗干预的需要,临床医生应该意识到这种关联。
    UNASSIGNED: To report two cases of bilateral blepharokeratoconjunctivitis associated with hidradenitis suppurativa (HS).
    UNASSIGNED: Case report and literature review. The clinical courses of two patients with HS, including ocular presentation and medical management, are described.
    UNASSIGNED: Two female patients aged 18 and 23-years-old with severe HS presented with bilateral blepharokeratoconjunctivitis. Shared slit lamp findings included bilateral corneal neovascularization and inferior corneal thinning. Systemic immunosuppression was needed in the first case, which resulted in improvement in the patient\'s ophthalmic and dermatological findings.
    UNASSIGNED: We report two cases of bilateral blepharokeratoconjunctivitis in two patients with severe HS. To our knowledge, this association has not previously been described in the literature. Clinicians should be aware of this association given its potentially visually devastating manifestations and the need for early therapeutic interventions.
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  • 文章类型: Journal Article
    角膜新生血管形成(CoNV)主要由炎症过程引发,导致异常血管增殖和随之而来的视力损害。现有的CoNV治疗干预措施显示出有限的疗效和潜在的不良反应。卵白精氨酸甲基转移酶1(PRMT1)与炎症和M2巨噬细胞极化的调控有关。然而,PRMT1在CoNV中的确切机制仍不确定。这项研究探索了PRMT1抑制在碱烧伤诱导的CoNV小鼠模型中的影响。我们的发现表明PRMT1水平与角膜损伤之间存在直接关系。此外,我们的观察表明成纤维细胞生长因子2(FGF2)在CoNV中的表达增加,用PRMT1抑制剂治疗后降低。抑制PRMT1减轻角膜损伤和CoNV,角膜混浊和新生血管减少证明了这一点。免疫荧光分析和炎症因子表达评估表明,PRMT1抑制减弱M2巨噬细胞极化,通过施用重组FGF2蛋白而逆转的现象。这些结果通过在人脐静脉内皮细胞(HUVEC)和单核细胞巨噬细胞(RAW264.7)的小鼠白血病细胞上的实验得到证实。此外,已经确定FGF2在PI3K/Akt信号转导中起作用,M2巨噬细胞极化的关键调节途径。重要的是,发现该途径的活性被PRMT1抑制剂抑制。机械上,显示PRMT1促进M2巨噬细胞极化,从而有助于CoNV,通过FGF2/PI3K/Akt途径。因此,靶向PRMT1可能提供一种有希望的治疗方法.
    Corneal neovascularization (CoNV) is predominantly initiated by inflammatory processes, resulting in aberrant vascular proliferation and consequent visual impairment. Existing therapeutic interventions for CoNV demonstrate limited efficacy and potential for adverse reactions. Protein arginine methyltransferase 1 (PRMT1) is associated with the regulation of inflammation and M2 macrophage polarization. Nevertheless, the precise mechanism by which PRMT1 operates in CoNV remains uncertain. This study explored the impact of PRMT1 inhibition in a murine model of CoNV induced by alkali burn. Our findings indicated a direct relationship between PRMT1 levels and corneal damage. Moreover, our observations indicated an increase in fibroblast growth factor 2 (FGF2) expression in CoNV, which was reduced after treatment with a PRMT1 inhibitor. The inhibition of PRMT1 alleviated both corneal injury and CoNV, as evidenced by decreased corneal opacity and neovascularization. Immunofluorescence analysis and evaluation of inflammatory factor expression demonstrated that PRMT1 inhibition attenuated M2 macrophage polarization, a phenomenon that was reversed by the administration of recombinant FGF2 protein. These results were confirmed through experimentation on Human Umbilical Vein Endothelial Cells (HUVECs) and Mouse leukemia cells of monocyte macrophage cells (RAW264.7). Furthermore, it was established that FGF2 played a role in PI3K/Akt signal transduction, a critical regulatory pathway for M2 macrophage polarization. Importantly, the activity of this pathway was found to be suppressed by PRMT1 inhibitors. Mechanistically, PRMT1 was shown to promote M2 macrophage polarization, thereby contributing to CoNV, through the FGF2/PI3K/Akt pathway. Therefore, targeting PRMT1 may offer a promising therapeutic approach.
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  • 文章类型: Journal Article
    目的:本研究的目的是强调角膜新生血管(NV)的医学和外科治疗的最新进展。
    结果:临床医生对角膜NV的认识和诊断标准的提高导致了角膜NV的表征和通过辅助成像设备对治疗反应的客观评估的进步。角膜NV治疗的进展,如抗血管内皮生长因子,细针透热,光动力疗法,改善了治疗成功率和视觉结果。最近的手术治疗进展包括角膜交联,内皮角膜移植术,和丝裂霉素血管内化疗栓塞。最后,对角膜NV涉及的分子发病机制和血管生成因子的更多认识已经确定了未来许多潜在的靶向治疗.
    结论:角膜NV的管理已经发展到包括几个独立的和组合的医疗和手术选择。此外,在角膜NV的量化和对其分子基础的理解方面的改进有助于新的治疗策略,改善结局.
    OBJECTIVE: The aim of this study was to highlight recent developments in the medical and surgical management of corneal neovascularization (NV).
    RESULTS: Improved understanding and diagnostic criteria among clinicians have led to advancements in the characterization of corneal NV and objective assessment of treatment response through ancillary imaging devices. Developments in corneal NV treatments, such as antivascular endothelial growth factor, fine needle diathermy, and photodynamic therapy, have improved treatment success rates and visual outcomes. More recent surgical treatment advancements include corneal cross-linking, endothelial keratoplasty, and mitomycin intravascular chemoembolization. Finally, a greater appreciation of the molecular pathogenesis and angiogenic factors involved in corneal NV has identified numerous potential targeted therapies in the future.
    CONCLUSIONS: The management of corneal NV has evolved to include several standalone and combination medical and surgical options. Additionally, improvements in quantifying corneal NV and understanding its molecular basis have contributed to new management strategies with improved outcomes.
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  • 文章类型: Journal Article
    角膜新生血管(CNV)是世界范围内常见的致盲因素之一。导致视力下降甚至失明。然而,目前的治疗方法如手术干预和抗VEGF药物治疗仍存在一些不足或引起一些不良反应。最近,SU6668,一种靶向血管生成酪氨酸激酶的抑制剂,已经证明了对新血管形成的生长抑制。但其疏水性和低的眼部生物利用度限制了其在角膜中的应用。特此,我们建议使用超稳定的纯纳米药物配方技术(SPFT)制备SU6668纯纳米颗粒(NanoSU6668;尺寸〜135nm),在1mg/mL时具有均匀的粒径和优异的水分散体。此外,将间充质干细胞膜囊泡(MSCm)包被在NanoSU6668表面,然后与TAT细胞穿透肽偶联,制备多功能TAT-MSCm@NanoSU6668(T-MNS)。通过滴眼液处理浓度为200µg/mL的T-MNS的CNV,并以高靶向性能积聚在血管中,治疗4天后可消除血管并恢复角膜透明度。同时,药物安全性测试证实,T-MNS没有对角膜造成任何损害,视网膜和其他眼组织。总之,T-MNS滴眼液具有在低给药频率下有效和安全地治疗CNV的潜力,为CNV疗法开辟了新天地。
    Corneal neovascularization (CNV) is one of the common blinding factors worldwide, leading to reduced vision or even blindness. However, current treatments such as surgical intervention and anti-VEGF agent therapy still have some shortcomings or evoke some adverse effects. Recently, SU6668, an inhibitor targeting angiogenic tyrosine kinases, has demonstrated growth inhibition of neovascularization. But the hydrophobicity and low ocular bioavailability limit its application in cornea. Hereby, we proposed the preparation of SU6668 pure nanoparticles (NanoSU6668; size ~135 nm) using a super-stable pure-nanomedicine formulation technology (SPFT), which possessed uniform particle size and excellent aqueous dispersion at 1 mg/mL. Furthermore, mesenchymal stem cell membrane vesicle (MSCm) was coated on the surface of NanoSU6668, and then conjugated with TAT cell penetrating peptide, preparing multifunctional TAT-MSCm@NanoSU6668 (T-MNS). The T-MNS at a concentration of 200 µg/mL was treated for CNV via eye drops, and accumulated in blood vessels with a high targeting performance, resulting in elimination of blood vessels and recovery of cornea transparency after 4 days of treatment. Meanwhile, drug safety test confirmed that T-MNS did not cause any damage to cornea, retina and other eye tissues. In conclusion, the T-MNS eye drop had the potential to treat CNV effectively and safely in a low dosing frequency, which broke new ground for CNV theranostics.
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  • 文章类型: Journal Article
    角膜新生血管形成会损害视力并导致生活质量差。发病机制涉及血管生成因子的复杂相互作用,血管内皮生长因子(VEGF)。这篇综述提供了角膜新生血管的潜在治疗的全面概述。涵盖金属蛋白酶(TIMPs)的组织抑制剂,转化生长因子β(TGF-β)抑制剂,白细胞介素-1L受体拮抗剂(IL-1Ra),一氧化氮合酶(NOS)亚型,半乳糖凝集素-3抑制剂,视网膜色素上皮衍生因子(PEDF),血小板衍生生长因子(PDGF)受体抑制剂,和手术治疗。常规治疗包括抗VEGF治疗和激光治疗,而新兴的治疗如免疫抑制药物(环孢素和雷帕霉素)已经被探索。氯沙坦和核心蛋白聚糖是减轻TGF-β诱导的纤维化的潜在抗纤维化药物。眼部纳米系统是促进治疗剂靶向释放的创新药物递送平台。基因疗法,如小干扰RNA和反义寡核苷酸,是选择性抑制血管生成相关基因表达的有前途的方法。Aganirsen在减少角膜新生血管形成面积方面是有效的,而没有显著的副作用。这些多方面的方法强调了角膜新生血管化管理的复杂性,并突出了提高治疗效果的想法。此外,讨论了联合治疗的重要性以及需要进一步研究以开发特异性抑制剂,同时考虑其治疗效果和潜在的不良反应.
    Corneal neovascularization can impair vision and result in a poor quality of life. The pathogenesis involves a complex interplay of angiogenic factors, notably vascular endothelial growth factor (VEGF). This review provides a comprehensive overview of potential therapies for corneal neovascularization, covering tissue inhibitors of metalloproteinases (TIMPs), transforming growth factor beta (TGF-β) inhibitors, interleukin-1L receptor antagonist (IL-1 Ra), nitric oxide synthase (NOS) isoforms, galectin-3 inhibitors, retinal pigment epithelium-derived factor (PEDF), platelet-derived growth factor (PDGF) receptor inhibitors, and surgical treatments. Conventional treatments include anti-VEGF therapy and laser interventions, while emerging therapies such as immunosuppressive drugs (cyclosporine and rapamycin) have been explored. Losartan and decorin are potential antifibrotic agents that mitigate TGF-β-induced fibrosis. Ocular nanosystems are innovative drug-delivery platforms that facilitate the targeted release of therapeutic agents. Gene therapies, such as small interfering RNA and antisense oligonucleotides, are promising approaches for selectively inhibiting angiogenesis-related gene expression. Aganirsen is efficacious in reducing the corneal neovascularization area without significant adverse effects. These multifaceted approaches underscore the corneal neovascularization management complexity and highlight ideas for enhancing therapeutic outcomes. Furthermore, the importance of combination therapies and the need for further research to develop specific inhibitors while considering their therapeutic efficacy and potential adverse effects are discussed.
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  • 文章类型: Journal Article
    目的:报道一例与人乳头瘤病毒(HPV)-16感染相关的眼表鳞状细胞瘤(OSSN)的罕见病例,该病例在年轻的健康患者中具有非典型形态。
    方法:一名17岁的健康男性被转诊到我们的部门,以评估右眼前基质新生血管形成的角膜浸润。一年前,患者接受了角膜结膜病变的切除,该病变位于同一只眼睛的下方。组织病理学分析显示结膜上皮中度和重度发育不良,并导致HPV-16阳性。我们使用聚合酶链反应(PCR)对结膜和角膜上皮进行了诊断性切开活检,以进行组织学检查和HPV和衣原体的分子检测。组织病理学评估显示结膜低度发育不良。与另一个中心进行的首次活检相似,角膜上皮的PCR检测对HPV-16呈阳性。该患者用局部干扰素α-2b(1,000,000IU/ml)成功治疗总共6个月。治疗后,随着新生血管形成的消退以及角膜透明度和视力的改善,角膜浸润显着改善。
    结论:本报告描述了HPV相关OSSN的非典型表现,因为其形态异常,发病年龄小,没有相关的合并症。
    结论:采用局部干扰素-α2b保守治疗可成功治疗HPV-16阳性OSSN,与手术切除相比,没有角膜不规则或潜在的视力丧失。
    OBJECTIVE: To report an unusual case of ocular surface squamous neoplasia (OSSN) associated with human papilloma virus (HPV)-16 infection with an atypical morphology in a young otherwise healthy patient.
    METHODS: A 17 year-old healthy male was referred to our department for evaluation of a corneal infiltrate with anterior stromal neovascularization in the right eye. One year before, the patient underwent an excision of a corneo-conjunctival lesion that was located inferiorly in the same eye. Histopathological analysis had shown moderate and severe dysplasia of the conjunctival epithelium and resulted positive for HPV-16. We performed a diagnostic incisional biopsy of the limbal conjunctiva and of the corneal epithelium for histological examination and molecular testing for HPV and Chlamydia by using polymerase chain reaction (PCR). Histopathologic evaluation demonstrated low-grade dysplasia of conjunctiva. PCR testing of the corneal epithelium was positive for HPV-16, similarly to the first biopsy performed by another centre. The patient was successfully treated with topical interferon alfa-2b (1,000,000 IU/ml) for a total of six months. After the treatment, the corneal infiltrate improved dramatically with regression of neovascularization and improvement of corneal transparency and vision.
    CONCLUSIONS: The present report described an atypical presentation of HPV-related OSSN due to its unusual morphology, young age of onset and absence of associated comorbidity.
    CONCLUSIONS: Conservative treatment with topical interferon-alpha 2b could be used to treat successfully HPV-16 positive OSSN, with no corneal irregularity or potential loss of vision compared to surgical excision.
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  • 文章类型: Journal Article
    角膜新生血管形成(CoNV)是一种威胁视力的眼部疾病,通常继发于感染性疾病,炎症,和创伤性病因。裂隙灯摄影,体内共聚焦显微镜,血管造影,光学相干断层扫描血管造影(OCTA)是临床实践中用于评估眼表脉管系统的主要诊断工具。然而,目前缺乏全面的文献来回顾CoNV给药的成像技术的进步.最初设计用于视网膜血管成像,OCTA现已扩展到前段,并显示出结膜成像的潜力,角膜,还有虹膜.这种扩展允许定量监测与CoNV相关的结构和功能变化。在这次审查中,我们强调眼前节光学相干断层扫描血管造影(AS-OCTA)中算法优化对CoNV诊断效能的影响.通过对现有文献的分析,进一步报道了动物模型评估以研究其病理机制并表现出显着的治疗干预措施。总之,AS-OCTA在CoNV的临床诊断和研究应用中具有广阔的前景和广阔的潜力。
    Corneal neovascularization (CoNV) is a vision-threatening ocular disease commonly secondary to infectious, inflammatory, and traumatic etiologies. Slit lamp photography, in vivo confocal microscopy, angiography, and optical coherence tomography angiography (OCTA) are the primary diagnostic tools utilized in clinical practice to evaluate the vasculature of the ocular surface. However, there is currently a dearth of comprehensive literature that reviews the advancements in imaging technology for CoNV administration. Initially designed for retinal vascular imaging, OCTA has now been expanded to the anterior segment and has shown promising potential for imaging the conjunctiva, cornea, and iris. This expansion allows for the quantitative monitoring of the structural and functional changes associated with CoNV. In this review, we emphasize the impact of algorithm optimization in anterior segment-optical coherence tomography angiography (AS-OCTA) on the diagnostic efficacy of CoNV. Through the analysis of existing literature, animal model assessments are further reported to investigate its pathological mechanism and exhibit remarkable therapeutic interventions. In conclusion, AS-OCTA holds broad prospects and extensive potential for clinical diagnostics and research applications in CoNV.
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