CXCR3 deletion aggravates corneal neovascularization in a corneal alkali-burn model

Li, Shengguo; Shi, Shuizhen; Xia, Fan; Luo, Ban; Ha, Yonju; Luisi, Jonathan; Gupta, Praveena; Merkley, Kevin H.; Liu, Hua; Zhang, Wenbo

doi:10.1016/j.exer.2022.109265

Cited by 5 publications

(4 citation statements)

References 36 publications

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“…The mechanism of alkali burns involves distinct pathways of lymphangiogenesis regulatory factors compared to those involved in corneal graft rejection. One notable distinction is the upregulation of the CXCR system ( Li et al, 2022 ), which potentially leads to a reduction in the expression of VEGF-A and VEGF-C. Additionally, as the inflammatory response subsides, the secretion of VEGF-C decreases ( Shen et al, 2014 ). Notably, during the process of lymphatic flap formation, the involvement of EphB4 receptor tyrosine kinases and their transmembrane adrenergic B2 ligands assumes a crucial role under both conditions ( Lyons et al, 2021 ).…”

Section: Advances In Nascent Lymphatics In Multiple Ocular Diseasesmentioning

confidence: 99%

“…Previously, it was believed that the CXCR3 chemokine was expressed in newly formed blood vessels because it binds to CXCL10, where it controls the expression of VEGF-A and C and indirectly affects effectors such as MMP13 and Serpine1, thereby inhibiting the migration of endothelial cells and the formation of new lumina ( Gao et al, 2017 ). Therefore, inhibiting CXCR3 and thus attenuating VEGF expression while controlling the transition of endothelial cells to the nascent lymphatic vessel wall could also be a means of alleviating lymphangiogenesis and mitigating alkali burns; however, it is important to note that CXCR3 expression had no effect on lymphangiogenesis according to the study conducted by Li et al This finding may suggest that CXCR3 participates in distinct mechanisms during corneal angiogenesis and lymphangiogenesis ( Li et al, 2022 ), which need further investigation. EphB4 receptor tyrosine kinase and its transmembrane epinephrine B2 ligand-mediated signaling play critical roles in the formation and maintenance of flaps in corneal neoplastic vessels, and disruption of ephrinB2-EphB4 signaling interferes with the afferent arm of the immune reflex arc by affecting lymphatic flap formation and leukocyte-lymphoid interactions ( Katsuta et al, 2013 ) so that lymphangiogenesis is inhibited, thereby reducing alkali burn injury in the eye.…”

Section: Advances In Nascent Lymphatics In Multiple Ocular Diseasesmentioning

confidence: 99%

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New targets of nascent lymphatic vessels in ocular diseases

Wu,

Ma,

Zhang

et al. 2024

Front. Physiol.

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Recent advancements in the field of endothelial markers of lymphatic vessels and lymphangiogenic factors have shed light on the association between several ocular diseases and ocular nascent lymphatic vessels. The immune privilege of corneal tissue typically limits the formation of lymphatic vessels in a healthy eye. However, vessels in the eyes can potentially undergo lymphangiogenesis and be conditionally activated. It is evident that nascent lymphatic vessels in the eyes contribute to various ocular pathologies. Conversely, lymphatic vessels are present in the corneal limbus, ciliary body, lacrimal glands, optic nerve sheaths, and extraocular muscles, while a lymphatic vasculature-like system exists in the choroid, that can potentially cause several ocular pathologies. Moreover, numerous studies indicate that many ocular diseases can influence or activate nascent lymphatic vessels, ultimately affecting patient prognosis. By understanding the mechanisms underlying the onset, development, and regression of ocular nascent lymphatic vessels, as well as exploring related research on ocular diseases, this article aims to offer novel perspectives for the treatment of such conditions.

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Section: Advances In Nascent Lymphatics In Multiple Ocular Diseasesmentioning

confidence: 99%

Section: Advances In Nascent Lymphatics In Multiple Ocular Diseasesmentioning

confidence: 99%

New targets of nascent lymphatic vessels in ocular diseases

Wu,

Ma,

Zhang

et al. 2024

Front. Physiol.

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“…On account of its immunostimulatory properties, alkali burn is often used to produce corneal injury models for investigating the impact of gene knockout and various protein compounds on pathological corneal lymphangiogenesis [165,[203][204][205]. When used in combination with dual-transgenic imaging techniques, the corneal alkali injury murine model allows for simultaneous live visualization of blood and lymphatic vessel growth [206].…”

Section: Alkali Burnmentioning

confidence: 99%

Lymphangiogenesis Guidance Mechanisms and Therapeutic Implications in Pathological States of the Cornea

Patnam

Dommaraju

Masood

et al. 2023

Cells

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Corneal lymphangiogenesis is one component of the neovascularization observed in several inflammatory pathologies of the cornea including dry eye disease and corneal graft rejection. Following injury, corneal (lymph)angiogenic privilege is impaired, allowing ingrowth of blood and lymphatic vessels into the previously avascular cornea. While the mechanisms underlying pathological corneal hemangiogenesis have been well described, knowledge of the lymphangiogenesis guidance mechanisms in the cornea is relatively scarce. Various signaling pathways are involved in lymphangiogenesis guidance in general, each influencing one or multiple stages of lymphatic vessel development. Most endogenous factors that guide corneal lymphatic vessel growth or regression act via the vascular endothelial growth factor C signaling pathway, a central regulator of lymphangiogenesis. Several exogenous factors have recently been repurposed and shown to regulate corneal lymphangiogenesis, uncovering unique signaling pathways not previously known to influence lymphatic vessel guidance. A strong understanding of the relevant lymphangiogenesis guidance mechanisms can facilitate the development of targeted anti-lymphangiogenic therapeutics for corneal pathologies. In this review, we examine the current knowledge of lymphatic guidance cues, their regulation of inflammatory states in the cornea, and recently discovered anti-lymphangiogenic therapeutic modalities.

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“…It also inhibits neutrophil and macrophage infiltration and suppresses inflammation-related angiogenesis mediated by matrix metalloproteinase-2 (MMP-2). Besides, rapamycin inhibits inflammation induced by corneal alkali burns by regulating angiogenesis through HIF-1α/VEGF, serum cytokines TNF-α, IL-6, interferon-gamma (IFN-γ), and granulocyte-macrophage colony-stimulating factor (GM-CSF) [44]. The initial dose is 2 mg daily but can be modified depending on the clinical effect, no more often than every 7-14 days.…”

Section: Other Drugsmentioning

confidence: 99%

Update on Therapeutic Approaches to Corneal Neovascularisation

Drzyzga,

Śpiewak,

Wyględowska-Promieńska

2023

Preprint

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A healthy cornea is a nonvascularized, transparent tissue. It is nourished by diffusion through the tear film, aqueous fluid and neurotrophins supplied by the corneal innervation. The cornea is devoid of both blood and lymphatic vessels, which makes it an immunologi-cally privileged tissue. Corneal neovascularization develops due to an imbalance between angiogenic and anti-angiogenic factors and can lead to a significant decrease in visual acui-ty. It may cause scarring, lipid keratopathy, and corneal edema. The resulting pathological vascularization of the cornea reduces its immune privilege and significantly worsens the prognosis after subsequent penetrating keratoplasty, increasing the risk of rejection of the transplanted flap. Neovascularization is favored by many disease processes, including auto-immune diseases, viral inflammations, mainly herpes and varicella-zoster, and blepharitis [1]. There are several options to treat corneal neovascularization, both pharmacological and surgical. Angiostatic treatment involves inhibiting the growth of new vessels by suppressing inflammatory responses. VEGF inhibitors, steroids, cyclosporine A, and amniotic membrane grafts secured to the cornea work this way. VEGF inhibitors are the agents with the direct and most potent angiostatic effect. Angioregressive treatment, on the other hand, results in the regression of already existing pathological vessels. This therapy is also based on VEGF inhibitors, which, however, have the most potent effect on newly formed and small vessels but are less effective in reducing large-caliber and mature vessels. A more effective method for such vessels is ablation, which involves surgical closure. The most commonly used an-gio-occlusive method is needle diathermy and argon or yellow laser therapy. In advanced corneal neovascularization, corneal transplant surgery may be necessary. It is best performed after pretreatment with anti-VEGF preparations, often continued after corneal transplanta-tion to reduce the risk of transplant rejection [2]. This paper discusses the pathogenesis of corneal neovascularization and the current and future trends in its treatment.

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CXCR3 deletion aggravates corneal neovascularization in a corneal alkali-burn model

Cited by 5 publications

References 36 publications

New targets of nascent lymphatic vessels in ocular diseases

New targets of nascent lymphatic vessels in ocular diseases

Lymphangiogenesis Guidance Mechanisms and Therapeutic Implications in Pathological States of the Cornea

Update on Therapeutic Approaches to Corneal Neovascularisation

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