The Maintenance of Lymphatic Vessels in the Cornea Is Dependent on the Presence of Macrophages

Maruyama, Kouichi; Nakazawa, Toru; Cursiefen, Claus; Maruyama, Yuko; Rooijen, Nico van; D'Amore, Patricia A.; Kinoshita, Shigeru

doi:10.1167/iovs.11-8010

Cited by 58 publications

(44 citation statements)

References 35 publications

(42 reference statements)

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“…Interestingly, macrophages decreased in inflammatory corneas after CXL, which should contribute to the regression of pathologic BVs and LVs in corneas, as macrophages play a key role in the induction of angiogenesis44, 45 and lymphangiogenesis46, 47, 48, 49 under pathological conditions in the cornea and in the maintenance of LVs 50. Furthermore, we also observed significant reduction in CD45 + leukocytes in suture‐induced inflammation in corneas after CXL treatment using riboflavin and UVA.…”

Section: Discussionmentioning

confidence: 52%

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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Section: Discussionmentioning

confidence: 52%

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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“…For instance, CD11b+macrophages are required for corneal lymphangiogenesis under pathological conditions (Maruyama et al, 2005, 2012). Similarly, Th17 cells promote angiogenesis in autoimmune diseases and malignancies through IL-17 (Chauhan et al, 2011).…”

Section: Discussionmentioning

confidence: 99%

Inhibition of HUVEC tube formation via suppression of NFκB suggests an anti-angiogenic role for SLURP1 in the transparent cornea

Loughner

Swamynathan

2017

Experimental Eye Research

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Previously, we have reported that the Secreted Ly6/uPAR related protein-1 (SLURP1) serves an important immunomodulatory function in the ocular surface. Here, we examine the involvement of SLURP1 in regulating corneal angiogenic privilege. Slurp1 expression detected by QPCR, immunoblots and immunofluorescent stain, was significantly decreased in mouse corneas subjected to alkali burn-induced corneal neovascularization (CNV). Addition of exogenous SLURP1 (6XHis-tagged, E. coli expressed and partially purified using Ni-ion columns) significantly suppressed the tumor necrosis factor-α (TNF-α)- stimulated human umbilical cord vascular endothelial cell (HUVEC) tube formation. SLURP1 suppressed the HUVEC tube length, tube area and number of branch points, without affecting their viability and/or proliferation. Exogenous SLURP1 in HUVEC also suppressed the TNF-α-induced (i) interleukin-8 (IL-8) and TNF-α production, (ii) adhesion to different components of the extracellular matrix, (iii) migration, and (iv) nuclear localization of NFκB. Together, these results demonstrate that SLURP1 suppresses HUVEC tube formation by blocking nuclear translocation of NFκB, and suggest a potential role for SLURP1 in promoting corneal angiogenic privilege.

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“…In healthy corneas (Day 0), blood and lymphatic vessels were restricted to the limbus but some lymphatics extended in the cornea as previously described. 31 Three days after cauterization, significant hemangiogenesis was observed that persisted until day 21. This was followed by a strong blood vessel regression observed after 40 days.…”

Section: Time Course Corneal Lymph/angiogenesismentioning

confidence: 99%

Sunitinib Inhibits Inflammatory Corneal Lymphangiogenesis

Detry

Blacher

Erpicum

et al. 2013

Invest. Ophthalmol. Vis. Sci.

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The Maintenance of Lymphatic Vessels in the Cornea Is Dependent on the Presence of Macrophages

Cited by 58 publications

References 35 publications

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

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

Inhibition of HUVEC tube formation via suppression of NFκB suggests an anti-angiogenic role for SLURP1 in the transparent cornea

Sunitinib Inhibits Inflammatory Corneal Lymphangiogenesis

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