Role of Angiopoietin-2 in Corneal Lymphangiogenesis

Yuen, Don; Grimaldo, Sammy; Sessa, Roberto; Ecoiffier, Tatiana; Truong, Thai V.; Huang, Eric C.; Bernas, Michael; Daley, Sarah; Witte, Marlys H.; Chen, Lu

doi:10.1167/iovs.13-13779

Cited by 25 publications

(39 citation statements)

References 36 publications

(63 reference statements)

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“…16,19 Briefly, whole-mount corneas were fixed in acetone for immunofluorescent staining. Samples were sequentially incubated with purified rabbit-anti-mouse LYVE-1 (Abcam, Cambridge, MA, USA) and goat-anti-mouse Itga-9 antibodies (R&D Systems, Minneapolis, MN, USA), which were visualized by FITCconjugated donkey-anti-rabbit and Cy3-conjugated donkey-antigoat secondary antibodies (Jackson ImmunoResearch), respectively.…”

Section: Immunofluorescent Microscopic Assay and Lymphatic Valve Quanmentioning

confidence: 99%

“…The number of lymphatic valves per cornea was quantified and the percentage scores were obtained by normalizing to control groups where the scores were defined as being 100%. 16,19 Lymphatic Endothelial Cell Culture and Immunocytofluorescent Microscopic Assay…”

Section: Immunofluorescent Microscopic Assay and Lymphatic Valve Quanmentioning

confidence: 99%

“…13,19 Briefly, human neonatal microdermal LECs were purchased from Lonza (Walkersville, MD, USA) and maintained in EGM-2MV cell culture medium (Lonza) according to manufacturer's instructions. For LEC staining, cells were incubated with rabbit anti-human-Itga-9 antibody (Novus Biologicals, Littleton, CO, USA) and visualized by Cy3-conjugated donkey-anti-rabbit secondary antibody (Jackson ImmunoResearch).…”

Section: Immunofluorescent Microscopic Assay and Lymphatic Valve Quanmentioning

confidence: 99%

“…13,19 Custom-designed siRNA duplexes were synthesized by Qiagen (Valencia, CA, USA) against human Itga-9 mRNA (5 0 -AAG AAG AAA GTC GTA CTA TAG-3 0 ). Scrambled siRNA control was purchased from Ambion (Austin, TX, USA).…”

Section: Sirna Transfectionmentioning

confidence: 99%

“…13,19,20 Total RNA was extracted and purified from LECs 48 hours after siRNA transfection with an RNAeasy mini-kit from Qiagen. Reverse transcription was performed using the SuperScript VILO cDNA synthesis kit from Invitrogen.…”

Section: Reverse Transcription and Real-time Pcrmentioning

confidence: 99%

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Integrin Alpha-9 Mediates Lymphatic Valve Formation in Corneal Lymphangiogenesis

Altiok

Ecoiffier

Sessa

et al. 2015

Invest. Ophthalmol. Vis. Sci.

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PURPOSE. We recently reported that corneal lymphatic vessels develop integrin alpha-9 (Itga-9)-positive valves during inflammatory lymphangiogenesis. The purpose of this study was to further investigate the role of Itga-9 in corneal lymphatic valve formation in vivo and lymphatic endothelial cell (LEC) functions in vitro. METHODS.Standard murine suture placement model was used to study the effect of Itga-9 blockade on lymphatic valve formation in vivo using Itga-9 neutralizing antibody. Wholemount corneas were harvested for immunofluorescent microscopic analysis. Additionally, human LEC culture system was used to examine the effect of Itga-9 gene knockdown on cell functions using small interfering RNAs (siRNAs).RESULTS. Itga-9 blockade in vivo significantly reduced the number of lymphatic valves formed in the inflamed cornea. Moreover, Itga-9 gene knockdown in human LECs suppresses cell functions of proliferation, adhesion, migration, and tube formation.CONCLUSIONS. Itga-9 is critically involved in corneal lymphatic valve formation. Further investigation of the Itga-9 pathway may provide novel strategies to treat lymphatic-related diseases occurring both inside and outside the eye.

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Section: Immunofluorescent Microscopic Assay and Lymphatic Valve Quanmentioning

confidence: 99%

Section: Immunofluorescent Microscopic Assay and Lymphatic Valve Quanmentioning

confidence: 99%

Section: Immunofluorescent Microscopic Assay and Lymphatic Valve Quanmentioning

confidence: 99%

Section: Sirna Transfectionmentioning

confidence: 99%

Section: Reverse Transcription and Real-time Pcrmentioning

confidence: 99%

See 3 more Smart Citations

Integrin Alpha-9 Mediates Lymphatic Valve Formation in Corneal Lymphangiogenesis

Altiok

Ecoiffier

Sessa

et al. 2015

Invest. Ophthalmol. Vis. Sci.

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Engineering the Lymphatic Network: A Solution to Lymphedema

Jia

Hitchcock-Szilagyi

et al. 2021

Adv Healthcare Materials

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Secondary lymphedema is a life‐long disorder characterized by chronic tissue swelling and inflammation that obstruct interstitial fluid circulation and immune cell trafficking. Regenerating lymphatic vasculatures using various strategies represents a promising treatment for lymphedema. Growth factor injection and gene delivery have been developed to stimulate lymphangiogenesis and augment interstitial fluid resorption. Using bioengineered materials as growth factor delivery vehicles allows for a more precisely targeted lymphangiogenic activation within the injured site. The implantation of prevascularized lymphatic tissue also promotes in situ lymphatic capillary network formation. The engineering of larger scale lymphatic tissues, including lymphatic collecting vessels and lymph nodes constructed by bioengineered scaffolds or decellularized animal tissues, offers alternatives to reconnecting damaged lymphatic vessels and restoring lymph circulation. These approaches provide lymphatic vascular grafting materials to reimpose lymphatic continuity across the site of injury, without creating secondary injuries at donor sites. The present work reviews molecular mechanisms mediating lymphatic system development, approaches to promoting lymphatic network regeneration, and strategies for engineering lymphatic tissues, including lymphatic capillaries, collecting vessels, and nodes. Challenges of advanced translational applications are also discussed.

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Kaposiform lymphangiomatosis treated with multimodal therapy improves coagulopathy and reduces blood angiopoietin‐2 levels

Crane

Manfredo

Boscolo

et al. 2020

Pediatric Blood & Cancer

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Kaposiform lymphangiomatosis (KLA) is a rare, life‐threatening congenital lymphatic malformation. Diagnosis is often delayed due to complex indistinct symptoms. Blood angiopoietin‐2 (ANG2) levels are elevated in KLA and may be useful as a biomarker to monitor disease status. We report a 7‐year‐old male child with easy bruising, inguinal swelling, and consumptive coagulopathy, diagnosed with KLA. A multimodal treatment regimen of prednisone, sirolimus, vincristine, and adjunctive zoledronate was used. Plasma ANG2 levels were highly elevated at diagnosis but decreased during treatment. The patient showed significant clinical improvement over a 38‐month period and normalization of ANG2 levels correlated with resolution of the coagulopathy.

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Role of Angiopoietin-2 in Corneal Lymphangiogenesis

Abstract: Angiopoietin-2 is critically involved in lymphatic processes in vivo and in vitro. Further investigation of the Ang-2 pathway may provide novel insights and therapeutic strategies for lymphatic-related disorders, which occur both inside and outside the eye.

Cited by 25 publications

References 36 publications

Integrin Alpha-9 Mediates Lymphatic Valve Formation in Corneal Lymphangiogenesis

Integrin Alpha-9 Mediates Lymphatic Valve Formation in Corneal Lymphangiogenesis

Engineering the Lymphatic Network: A Solution to Lymphedema

Kaposiform lymphangiomatosis treated with multimodal therapy improves coagulopathy and reduces blood angiopoietin‐2 levels

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