Time Course of Angiogenesis and Lymphangiogenesis After Brief Corneal Inflammation

Cursiefen, Claus; Maruyama, Kouichi; Jackson, David G.; Streilein, J. Wayne; Kruse, Friedrich E.

doi:10.1097/01.ico.0000183485.85636.ff

Cited by 168 publications

(166 citation statements)

References 21 publications

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“…Since this new technology enables simultaneous observation and tracking of both vessel types, it offers an excellent platform to identify the similarities and disparities between the two vascular systems in response to a stimulus. For example, although not a focus of this study, it was noted that the inflamed lymphatic vessels regressed earlier than blood vessels (arrowheads in Figure 1A and 1B) within live cornea, similarly as reported previously with the immunohistochemistry method [10].…”

Section: Dear Editorsupporting

confidence: 61%

Live imaging of newly formed lymphatic vessels in the cornea

Yuen

Kwan

et al. 2011

Cell Res

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Section: Dear Editorsupporting

confidence: 61%

Live imaging of newly formed lymphatic vessels in the cornea

Yuen

Kwan

et al. 2011

Cell Res

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“…noted the persistence of perfused capillaries as long as 8 months after removal of an inflammatory stimulus present for 14 days in the mouse cornea [11]. Compared with the 7-day period of inflammation in this study, a longer period can be expected to result in greater pericyte coverage of vessels [13] and their subsequent persistence for an indefinite period.…”

Section: In Vivo Imaging Of Human Corneal Capillary Regression: Repormentioning

confidence: 55%

Cellular level characterization of capillary regression in inflammatory angiogenesis using an in vivo corneal model

2011

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Abstract:In this study, we introduce a technique for repeated, microscopic observation of single regressing capillaries in vivo in inflamed murine corneas. Natural capillary regression was initiated by removal of inflammatory stimulus during an active pro-angiogenic phase, while the additional impact of anti-angiogenic treatment with triamcinolone or bevazicumab was investigated. Capillaries regressed naturally within one week and treatments did not further enhance the natural regression. Morphologically, early-phase regression was characterized by significant lumen narrowing and a significant reduction in CD11b+ myeloid cell infiltration of the extracellular matrix. By one week, vascular remodeling occurred concomitant with CD11b+CD68+KiM2R+ mature macrophage localization on capillary walls. Empty conduits without blood flow, positive for collagen IV and devoid of vascular endothelium and pericytes, were apparent in vivo and by three weeks were more numerous than perfused capillaries. By three weeks, macrophages aggregated around remaining perfused capillaries and were observed in apposition with degrading capillary segments. Abrupt termination of capillary sprouting in our regression model further revealed vascular endothelial abandonment of sprout tips and perfused capillary loop formation within a single angiogenic sprout, possibly as an intussusceptive response to cessation of the stimulus. Finally, we observed lumen constriction and macrophage localization on capillary walls in vivo in a clinical case of corneal capillary regression that paralleled findings in our murine model.

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“…The inflammatory insult brought about by the insertion of a silk suture into the stroma triggered not only the growth of new blood vessels (hemangiogenesis) into the cornea but also the growth of lymph vessels (lymphangiogenesis) (Cursiefen et al, 2006). Several studies have demonstrated that these two processes occur in parallel and are driven by the inflammatory response and more specifically by activated macrophages (Maruyama et al, 2005).…”

Section: Amplified Neovascular Response In Corneas Of Ho-2 Null Micementioning

confidence: 99%

Exacerbated corneal inflammation and neovascularization in the HO-2 null mice is ameliorated by biliverdin

Bellner

Vitto

Patil

et al. 2008

Experimental Eye Research

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Heme oxygenase (HO-1 and HO-2) represents an intrinsic cytoprotective and anti-inflammatory system based on its ability to modulate leukocyte migration and to inhibit expression of inflammatory cytokines and proteins. HO-2 deletion leads to unresolved corneal inflammation and chronic inflammatory complications including ulceration, perforation and neovascularization. We examined the consequences of HO-2 deletion on hemangiogenesis and lymphangiogenesis in the model of suture-induced inflammatory neovascularization. A 8.0 silk suture was placed at the corneal apex of wild type and HO-2 null mice. Neovascularization was assessed by vital microscopy and quantified by image analysis. Hemangiogenesis and lymphangiogenesis were determined by immunofluorescence staining using anti-CD31 and anti-LYVE-1 antibodies, respectively. Inflammation was quantified by histology and myeloperoxidase activity. The levels of HO-1 expression and inflammatory cytokines were determined by real time PCR and ELISA, respectively. Corneal sutures produced a consistent inflammatory response and a time-dependent neovascularization. The response in HO-2 null mice was associated with a greater increase compared to the wild type in the number of leukocytes (827600±129000 vs. 294500±57510; p<0.05), neovessels measured by vital microscopy (21.91±1.05 vs. 12.77±1.55 mm; p<0.001) 4 days after suture placement. Hemangiogenesis but not lymphangiogenesis was more pronounced in HO-2 null mice compared to wild type mice. Induction of HO-1 in sutured corneas was greatly attenuated in HO-2 null corneas and treatment with biliverdin diminished the exaggerated inflammatory and neovascular response in HO-2 null mice. The demonstration that the inflammatory responses, including expression of proinflammatory proteins, inflammatory cell influx and hemangiogenesis are exaggerated in HO-2 knockout mice strongly supports the notion that the HO system is critical for controlling the inflammatory and neovascular response in the cornea. Hence, pharmacological amplification of this system may constitute a novel therapeutic strategy for the treatment of corneal disorders associated with excessive inflammation and neovascularization.

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Time Course of Angiogenesis and Lymphangiogenesis After Brief Corneal Inflammation

Cited by 168 publications

References 21 publications

Live imaging of newly formed lymphatic vessels in the cornea

Live imaging of newly formed lymphatic vessels in the cornea

Cellular level characterization of capillary regression in inflammatory angiogenesis using an in vivo corneal model

Exacerbated corneal inflammation and neovascularization in the HO-2 null mice is ameliorated by biliverdin

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