Novel anti(lymph)angiogenic treatment strategies for corneal and ocular surface diseases

Bock, Felix; Maruyama, Kouichi; Regenfuß, Birgit; Hos, Deniz; Steven, Philipp; Heindl, Ludwig M.; Cursiefen, Claus

doi:10.1016/j.preteyeres.2013.01.001

Cited by 160 publications

(138 citation statements)

References 229 publications

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“…Similar inhibitors may prove useful in tissue transplantation, as inhibition of VEGFR3 signaling suppresses tissue allograft-induced lymphangiogenesis and improves graft survival in mouse models (11,12,(93)(94)(95). Notably, the neo-lymphatic vessels induced in tumors or allografts are not only passive conduits; they also secrete chemokines such as CCL21 to attract tumor cells or immune cells (95)(96)(97)(98).…”

Section: Translation Of Lymphangiogenic Mechanisms Into Therapeuticsmentioning

confidence: 99%

Lymphangiogenic factors, mechanisms, and applications

Zheng¹,

Aspelund²,

Alitalo³

2014

J. Clin. Invest.

270

244

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Lymphangiogenesis, the growth of lymphatic vessels, is essential in embryonic development. In adults, it is involved in many pathological processes such as lymphedema, inflammatory diseases, and tumor metastasis. Advances during the past decade have dramatically increased the knowledge of the mechanisms of lymphangiogenesis, including the roles of transcription factors, lymphangiogenic growth factors and their receptors, and intercellular and intracellular signaling cascades. Strategies based on these mechanisms are being tested in the treatment of various human diseases such as cancer, lymphedema, and tissue allograft rejection. This Review summarizes the recent progress on lymphangiogenic mechanisms and their applications in disease treatment.

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Section: Translation Of Lymphangiogenic Mechanisms Into Therapeuticsmentioning

confidence: 99%

Lymphangiogenic factors, mechanisms, and applications

Zheng¹,

Aspelund²,

Alitalo³

2014

J. Clin. Invest.

270

244

View full text Add to dashboard Cite

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“…Some studies have shown that interference with lymphatic function suppresses lymphangiogenesis and prolongs graft survival (52,83). Other studies, using an experimental corneal graft model, identified early post-transplantation lymphangiogenesis as a significant risk factor for immune rejection after keratoplasty, which can be reduced with postoperative anti-angiogenic/antilymphangiogenic treatments (84)(85)(86).…”

Section: Transplantation and Rejectionmentioning

confidence: 99%

“…Near complete regression of pathologic corneal lymphatic vessels was observed six months after suture-induced corneal lymphangiogenesis was established in mice (89). This implies that the keratoplasty procedure for patients with a history of corneal inflammation should be delayed, if possible, to secure an inflammation-free interval (86,89).…”

Section: Transplantation and Rejectionmentioning

confidence: 99%

Inflammation-associated lymphangiogenesis: a double-edged sword?

Kim¹,

Kataru²,

Koh³

2014

J. Clin. Invest.

189

146

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Lymphangiogenesis and lymphatic vessel remodeling are complex biological processes frequently observed during inflammation. Accumulating evidence indicates that inflammation-associated lymphangiogenesis (IAL) is not merely an endpoint event, but actually a phenomenon actively involved in the pathophysiology of various inflammatory disorders. The VEGF-C/VEGFR-3 and VEGF-A/VEGF-R2 signaling pathways are two of the best-studied pathways in IAL. Methods targeting these molecules, such as prolymphangiogenic or antilymphatic treatments, were found to be beneficial in various preclinical and/or clinical studies. This Review focuses on the most recent achievements in the fields of lymphatic biology relevant to inflammatory conditions. Additionally, preclinical and clinical therapies that modulate IAL are summarized.

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“…This avascular privilege can be disturbed by several corneal disorders and hypoxic diseases, followed by the ingrowth of pathologic BVs and LVs into the physiologically transparent corneal center 2. These pathologic corneal BVs and LVs can deteriorate visual acuity and lead to corneal blindness.…”

Section: Introductionmentioning

confidence: 99%

UV light crosslinking regresses mature corneal blood and lymphatic vessels and promotes subsequent high-risk corneal transplant survival

Hou

Tóth

et al. 2018

American Journal of Transplantation

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Immunologic graft rejection is the main complication after corneal transplant into pathologically prevascularized so‐called high‐risk eyes. The aim of this study was to evaluate whether ultraviolet (UV) light crosslinking can regress pathologic corneal blood and lymphatic vessels and thereby improve subsequent graft survival. Using the murine model of suture‐induced corneal neovascularization, we found that corneal crosslinking with UVA light and riboflavin regressed both preexisting blood and lymphatic vessels significantly via induction of apoptosis in vascular endothelial cells. In addition, macrophages and CD45+ cell counts were significantly reduced. Consistently, corneal crosslinking reduced keratocyte density and corneal thickness without affecting corneal nonvascular endothelial cells, iris, and lens depending on the crosslinking duration. Furthermore, using the murine model of corneal transplant, long‐term graft survival was significantly promoted (P < .05) and CD4+ CD25+FoxP3+ T regulatory cells were upregulated (P < .01) in high‐risk eyes preoperatively treated with crosslinking. Our results suggest UV light crosslinking as a novel method to regress both pathologic corneal blood and lymphatic vessels and to reduce CD45+ inflammatory cells. Furthermore, this study demonstrates for the first time that preoperative corneal crosslinking in prevascularized high‐risk eyes can significantly improve subsequent graft survival and may become a promising novel therapy in the clinic.

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Novel anti(lymph)angiogenic treatment strategies for corneal and ocular surface diseases

Cited by 160 publications

References 229 publications

Lymphangiogenic factors, mechanisms, and applications

Lymphangiogenic factors, mechanisms, and applications

Inflammation-associated lymphangiogenesis: a double-edged sword?

UV light crosslinking regresses mature corneal blood and lymphatic vessels and promotes subsequent high-risk corneal transplant survival

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