Vascular Endothelial Growth Factor Receptor 1 Morpholino Increases Graft Survival in a Murine Penetrating Keratoplasty Model

Cho, Yang Kyung; Zhang, Xiaohui; Uehara, Hironori; Young, Jason R.; Archer, Bonnie; Ambati, Balamurali K.

doi:10.1167/iovs.12-10408

Cited by 26 publications

(26 citation statements)

References 41 publications

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“…Lately, there have also been novel approaches to immunomodulate alloimmunity that have focused on morpholine oligonucleoitides, 32 cell-specific gene therapy, 34 RNA interference, 146 and anti-VEGF therapy, 162 with promising experimental results.…”

Section: Novel Strategies For Immunomodulation In Corneal Transplamentioning

confidence: 99%

Management of high-risk corneal transplantation

Zazzo

Kheirkhah

Abud

et al. 2017

Survey of Ophthalmology

120

102

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The cornea is the most commonly transplanted tissue in medicine. The main cause of corneal graft failure is allograft rejection. The incidence of graft rejection depends on the presence of high-risk characteristics, most notably corneal neovascularization. Although corneal graft has high success rates in the absence of these risk factors, high-risk keratoplasty is associated with low success rates due to a high incidence of immune-mediated graft rejection. To improve the survival of high-risk corneal transplantation, various preoperative, intraoperative, and postoperative measures can be considered. However, the key step in the management of these grafts is the long-term use of local and/or systemic immunosuppressive agents. Although a number of immunosuppressive agents have been employed for this purpose, the results vary significantly across different studies. This is partly due to the lack of an optimized method for their use as well as the lack of a precise stratification of the degree of risk in each individual patient. New targeted biologic treatments as well as tolerance-inducing methods show promising horizons in the management of high-risk corneal transplantation in near future.

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Section: Novel Strategies For Immunomodulation In Corneal Transplamentioning

confidence: 99%

Management of high-risk corneal transplantation

Zazzo

Kheirkhah

Abud

et al. 2017

Survey of Ophthalmology

120

102

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“…43 A new recombinant fusion protein, named aflibercept [or VEGF-Trap (R1R2) ], has also been developed recently for antiangiogenic therapy. Aflibercept recombinant fusion protein has two main components; the VEGF-binding portions from the extracellular domains of human VEGF receptors 1 and 2 are further fused to the Fc portion of human immunoglobulin 1 to form the antibody.…”

Section: Soluble or Modified Vegf Receptorsmentioning

confidence: 99%

Corneal neovascularization and contemporary antiangiogenic therapeutics

Hsu

Chang

Lin

et al. 2015

Journal of the Chinese Medical Association

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Corneal neovascularization (NV), the excessive ingrowth of blood vessels from conjunctiva into the cornea, is a common sequela of disease insult that can lead to visual impairment. Clinically, topical steroid, argon laser photocoagulation, and subconjunctival injection of bevacizumab have been used to treat corneal NV. Sometimes, the therapies are ineffective, especially when the vessels are large. Large vessels are difficult to occlude and easily recanalized. Scientists and physicians are now dedicated to overcoming this problem. In this article, we briefly introduce the pathogenesis of corneal NV, and then highlight the existing animal models used in corneal NV research-the alkali-induced model and the suture-induced model. Most of all, we review the potential therapeutic targets (i.e., vascular endothelial growth factor and platelet-derived growth factor) and their corresponding inhibitors, as well as the immunosuppressants that have been discovered in recent years by corneal NV studies.

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“…Cho et al reported that combining steroid treatment with VEGFR-1 morpholino, a synthetically produced molecule that binds mRNA to inhibit translation or alternative splicing, decreases both angiogenesis and lymphangiogenesis and improves corneal graft survival in a high-risk corneal transplantation murine model. 194 In addition, a combination of Flt23k nanoparticles that deliver plasmids expressing anti-VEGF intrareceptor Flt23k and steroid treatment significantly reduces lymphangiogenesis and improves graft survival in a mouse model of corneal transplantation. 195 …”

Section: Diseases Associated With Corneal Lymphangiogenesismentioning

confidence: 99%

Understanding lymphangiogenesis in knockout models, the cornea, and ocular diseases for the development of therapeutic interventions

Yang

Walia

Huang

et al. 2016

Survey of Ophthalmology

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A major focus of cancer research for several decades has been understanding the ability of tumors to induce new blood vessel formation, a process known as angiogenesis. Unfortunately, only limited success has been achieved in the clinical application of angiogenesis inhibitors. We now know that lymphangiogenesis, the growth of lymphatic vessels, likely also plays a major role in tumor progression. Thus, therapeutic strategies targeting lymphangiogenesis or both lymphangiogenesis and angiogenesis may represent promising approaches for treating cancer and other diseases. Importantly, research progress toward understanding lymphangiogenesis is significantly behind that related to angiogenesis. A PubMed search of ‘angiogenesis’ returns nearly 80,000 articles, whereas a search of ‘lymphangiogenesis’ returns approximately 2,635 articles. This stark contrast can be explained by the lack of molecular markers for identifying the invisible lymphatic vasculature that persisted until less than two decades ago combined with the intensity of research interest in angiogenesis during the past half-century. Still, significant strides have been made in developing strategies to modulate lymphangiogenesis, largely using ocular disease models. Here, we review the current knowledge of lymphangiogenesis in the context of knockout models, ocular diseases, the biology of activators and inhibitors, and the potential for therapeutic interventions targeting this process.

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Vascular Endothelial Growth Factor Receptor 1 Morpholino Increases Graft Survival in a Murine Penetrating Keratoplasty Model

Abstract: VEGFR1_MO decreased angiogenesis and lymphangiogenesis, resulting in increased graft survival in both NR PK and HR PK. This beneficial effect is synergistically enhanced with steroid treatment in HR PK.

Cited by 26 publications

References 41 publications

Management of high-risk corneal transplantation

Management of high-risk corneal transplantation

Corneal neovascularization and contemporary antiangiogenic therapeutics

Understanding lymphangiogenesis in knockout models, the cornea, and ocular diseases for the development of therapeutic interventions

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