Angiopoietin-2 Blockade Promotes Survival of Corneal Transplants

Zhang, Liwei; Li, Guangyu; Sessa, Roberto; Kang, Gyeong Jin; Shi, Meng; Ge, Shaokui; Gong, Anna Jiang; Wen, Yurong; Chintharlapalli, Sudhakar; Chen, Lu

doi:10.1167/iovs.16-20485

Cited by 14 publications

(12 citation statements)

References 18 publications

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“…The analysis was performed as previously reported. 21 – 24 For evaluation of central corneal thickness and peripheral anterior synechiae, an anterior-segment optical coherence tomography (OCT; Visante OCT MODEL 1000; Carl Zeiss Meditec, Dublin, CA, USA) was used. Quadrant-scans along four axes (0°–180°, 45°–225°, 90°–270°, and 135°–315°) were performed to ensure scanning through the central cornea and data along the 0° to 180° axis were used for analysis.…”

Section: Methodsmentioning

confidence: 99%

“…The experiment was performed as described previously. 24 Briefly, whole-mount limbal tissues were harvested at day 7 post-procedure, fixed in 4% paraformaldehyde, and immunostained with primary rat-anti-mouse CD31 antibody (BD Pharmingen, San Diego, CA, USA) that was visualized by Cy3-conjugated donkey anti-rat secondary antibody (Jackson-Immuno Research Laboratories, West Grove, PA, USA). Samples were mounted with Vectashield mounting medium (Vector Laboratories, Burlingame, CA, USA) and examined by an AxioImager M1 epifluorescence deconvolution microscope with AxioVision 4.8 software (Carl Zeiss AG, Göttingen, Germany).…”

Section: Methodsmentioning

confidence: 99%

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Establishment and Characterization of an Acute Model of Ocular Hypertension by Laser-Induced Occlusion of Episcleral Veins

Zhang

Shi

et al. 2017

Invest. Ophthalmol. Vis. Sci.

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PurposeThis study was designed to develop and characterize a laser-induced model of acute intraocular hypertension that permits the study of the anterior segment of the eye.MethodsCD1 mice aged 5 and 8 weeks were examined for elevation of IOP induced by laser photocoagulation. We compared between occlusion of episcleral veins alone and when combined with 270° limbal vessel occlusion. Anterior chamber angle, corneal thickness, and retinal nerve fiber layer (RNFL) thickness were evaluated by anterior- and posterior-segment optical coherence tomography (OCT). Additionally, at day 7 post-procedure, the anterior segment was evaluated for inflammatory cellular presentation by histologic analysis and OCT, and limbal vessels and whole-mount retina were immunostained for CD31 and Brn3a, respectively. Brn3a-positive retinal ganglion cells (RGCs) were quantified with ImageJ software.ResultsAfter single or combined laser treatment in mice aged 5 or 8 weeks, IOP was significantly elevated for 5 to 6 days before returning to the baseline by day 7 post-procedure. Anterior segment assessment indicated less synechiae in the anterior chamber angle and better preserved limbal vessels with single versus combined laser treatment. Corneal thickness was significantly increased after single or combined treatment. No inflammatory cells were detected in the anterior chamber. The thickness of the RNFL and the density of RGCs were both significantly reduced after single or combined treatment.ConclusionsLaser photocoagulation of episcleral veins alone in CD1 mice aged 5 to 8 weeks may be used to induce ocular hypertension resulting in RNFL thinning and ganglion cell loss. This model permits the study of the anterior as well as the posterior segment of the eye.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Establishment and Characterization of an Acute Model of Ocular Hypertension by Laser-Induced Occlusion of Episcleral Veins

Zhang

Shi

et al. 2017

Invest. Ophthalmol. Vis. Sci.

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“…The eye lymphatics may serve as a potential target for glaucoma therapy (1187), possibly using a VEGF-C therapy to expand drainage via Schlemm’s canal proposed (41, 523, 845). Anti-angiogenic/lymphangiogenic strategies may prove useful for corneal transplants (1207). In addition, better understanding of the lymphatics of the eye and surrounding orbit may help our with identifying new pharmacologic targets for metastatic disease involving the eye, or autoimmune disease involving the eye such as Graves disease (261).…”

Section: Organization and Anatomy Of The Lymphatic Systemmentioning

confidence: 99%

Lymphatic Vessel Network Structure and Physiology

Breslin

Yang

Scallan

et al. 2018

Comprehensive Physiology

274

258

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The lymphatic system is comprised of a network of vessels interrelated with lymphoid tissue, which has the holistic function to maintain the local physiologic environment for every cell in all tissues of the body. The lymphatic system maintains extracellular fluid homeostasis favorable for optimal tissue function, removing substances that arise due to metabolism or cell death, and optimizing immunity against bacteria, viruses, parasites, and other antigens. This article provides a comprehensive review of important findings over the past century along with recent advances in the understanding of the anatomy and physiology of lymphatic vessels, including tissue/organ specificity, development, mechanisms of lymph formation and transport, lymphangiogenesis, and the roles of lymphatics in disease.

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“…The same study found that TIE2 expression in cervical tumor cells is associated with significantly poor prognosis. Furthermore, treatment with Ang‐2 inhibitors significantly improves outcomes of corneal grafts …”

Section: Current Lymphangiogenesis Researchmentioning

confidence: 99%

“…Furthermore, treatment with Ang-2 inhibitors significantly improves outcomes of corneal grafts. 203 A recent report indicates that fatty acid -oxidation is required for lymphangiogenesis. Lymphangiogenesis is impaired in mice that lack carnitine palmitoyltransferase 1A (CPT1A), a rate-controlling enzyme in fatty acid oxidation.…”

Section: Current Lymphangiogenesis Researchmentioning

confidence: 99%

Potential lymphangiogenesis therapies: Learning from current antiangiogenesis therapies—A review

Yamakawa

Doh

Santosa

et al. 2018

Medicinal Research Reviews

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In recent years, lymphangiogenesis, the process of lymphatic vessel formation from existing lymph vessels, has been demonstrated to have a significant role in diverse pathologies, including cancer metastasis, organ graft rejection, and lymphedema. Our understanding of the mechanisms of lymphangiogenesis has advanced on the heels of studies demonstrating vascular endothelial growth factor C as a central pro-lymphangiogenic regulator and others identifying multiple lymphatic endothelial biomarkers. Despite these breakthroughs and a growing appreciation of the signaling events that govern the lymphangiogenic process, there are no FDA-approved drugs that target lymphangiogenesis. In this review, we reflect on the lessons available from the development of antiangiogenic therapies (26 FDA-approved drugs to date), review current lymphangiogenesis research including nanotechnology in therapeutic drug delivery and imaging, and discuss molecules in the lymphangiogenic pathway that are promising therapeutic targets.

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Angiopoietin-2 Blockade Promotes Survival of Corneal Transplants

Cited by 14 publications

References 18 publications

Establishment and Characterization of an Acute Model of Ocular Hypertension by Laser-Induced Occlusion of Episcleral Veins

Establishment and Characterization of an Acute Model of Ocular Hypertension by Laser-Induced Occlusion of Episcleral Veins

Lymphatic Vessel Network Structure and Physiology

Potential lymphangiogenesis therapies: Learning from current antiangiogenesis therapies—A review

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