Tie-2/Angiopoietin pathway modulation as a therapeutic strategy for retinal disease

Hussain, Rehan M.; Neiweem, Ashley E.; Kansara, Viral; Harris, Alon; Ciulla, Thomas A.

doi:10.1080/13543784.2019.1667333

Cited by 84 publications

(83 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Co-expression of Ang-2 and VEGF-A has been reported to produce accelerated neovascularization in the developing retina and ischemic retina models. Moreover, Ang-2 and VEGF levels have been reported elevated in vitreous samples from diabetic patients [ 16 ]. Levels of serum VEGF and Ang-2 are also found more elevated in proliferative diabetic retinopathy groups than in the non-proliferative diabetic retinopathy groups, suggesting that their levels may be related to the progression of retinopathy [ 17 ].…”

Section: Angiopoietin Biology and Signaling Literature Reviewmentioning

confidence: 99%

“…Reversal of Ang-1 and Ang-2 expression has been shown in malignancies. Thus increases in serum Ang-2 levels offer prognostic value for certain cancers and have been correlated with tumor progression, angiogenesis, metastasis, and patient survival [ 16 ]. Diabetic mouse models have supported that hyperglycemia also results in increased Ang-2 levels and expression of integrin α3 and β1 in pericytes, leading to pericyte apoptosis via the p53 pathway.…”

Section: Angiopoietin Biology and Signaling Literature Reviewmentioning

confidence: 99%

“…Angiopoietin-2 (Ang-2) serves many significant functions across vascular and extravascular settings. This is showcased well in disease conditions, such as hyperglycemia, hypoxia, or oxidative stress, where Ang-2 is markedly upregulated [ 16 ]. Diabetic macular edema (DME) and diabetic retinopathy, among other pathologic states, exemplifies the role of Ang-2 in stimulating pericyte loss, neovascularization, astrocyte loss in Blood-Brain Barrier (BBB), and breakdown of the Blood Retinal Barrier (BRB).…”

Section: Angiopoietin Biology and Signaling Literature Reviewmentioning

confidence: 99%

“…With the biological implications of angiopoietin and approaches described, faricimab (formerly RG7716), is the first bispecific antibody designed for intravitreal use, and can simultaneously bind to and neutralize Ang-2 and VEGF-A for treatment of nAMD and DME [ 16 , 59 , 60 ]. Patients with retinal vascular diseases deemed anti-VEGF sub-responders by retina specialists demonstrate a lack of visual acuity improvement or persistent anatomical symptoms, such as intra- or subretinal fluid.…”

Section: Clinical Studies Of Faricimab In Diabetic Macular Edemamentioning

confidence: 99%

See 3 more Smart Citations

Targeting Angiopoietin in Retinal Vascular Diseases: A Literature Review and Summary of Clinical Trials Involving Faricimab

Khan

Aziz

Shafi

et al. 2020

Cells

View full text Add to dashboard Cite

This review summarizes the latest findings in the literature of Angiopoietin-2 (Ang-2), Tyrosine-protein kinase receptor (Tie-2) complex, and faricimab along with their involvement for the treatment of retinal vascular diseases in various clinical trials. In ischemic diseases, such as diabetic retinopathy, Ang-2 is upregulated, deactivating Tie-2, resulting in vascular leakage, pericyte loss, and inflammation. Recombinant Angiopeotin-1 (Ang-1), Ang-2-blocking molecules, and inhibitors of vascular endothelial protein tyrosine phosphatase (VE-PTP) decrease inflammation-associated vascular leakage, showing therapeutic effects in diabetes, atherosclerosis, and ocular neovascular diseases. In addition, novel studies show that angiopoietin-like proteins may play an important role in cellular metabolism leading to retinal vascular diseases. Current therapeutic focus combines Ang-Tie targeted drugs with other anti-angiogenic or immune therapies. Clinical studies have identified faricimab, a novel bispecific antibody designed for intravitreal use, to simultaneously bind and neutralize Ang-2 and VEGF-A for treatment of diabetic eye disease. By targeting both Ang-2 and vascular endothelial growth factor-A (VEGF-A), faricimab displays an improved and sustained efficacy over longer treatment intervals, delivering superior vision outcomes for patients with diabetic macular edema and reducing the treatment burden for patients with neovascular age-related macular degeneration and diabetic macular edema. Phase 2 results have produced promising outcomes with regard to efficacy and durability. Faricimab is currently being evaluated in global Phase 3 studies.

show abstract

Section: Angiopoietin Biology and Signaling Literature Reviewmentioning

confidence: 99%

Section: Angiopoietin Biology and Signaling Literature Reviewmentioning

confidence: 99%

Section: Angiopoietin Biology and Signaling Literature Reviewmentioning

confidence: 99%

Section: Clinical Studies Of Faricimab In Diabetic Macular Edemamentioning

confidence: 99%

See 2 more Smart Citations

Targeting Angiopoietin in Retinal Vascular Diseases: A Literature Review and Summary of Clinical Trials Involving Faricimab

Khan

Aziz

Shafi

et al. 2020

Cells

View full text Add to dashboard Cite

show abstract

“…It is now clear that these molecules contribute to multiple other aspects of biology such as inflammation [17], cell survival [18], and cell migration and invasion [19]. Indeed, dysregulation of these molecules has been associated with a number of diseases including infection and septic shock [20,21], diabetes [22,23], and cancer [24,25]. In this article, we attempt to give an update reviewing recent literature on how Ang-1 and Ang-2 contribute to development and progression of cancer in general and neoplasia associated with viral infection.…”

Section: Introductionmentioning

confidence: 99%

Role of Angiopoietins in Development of Cancer and Neoplasia Associated with Viral Infection

2020

Cells

View full text Add to dashboard Cite

Angiopoietin/tyrosine protein kinase receptor Tie-2 signaling in endothelial cells plays an essential role in angiogenesis and wound healing. Angiopoietin-1 (Ang-1) is crucial for blood vessel maturation while angiopoietin-2 (Ang-2), in collaboration with vascular endothelial growth factor (VEGF), initiates angiogenesis by destabilizing existing blood vessels. In healthy people, the Ang-1 level is sustained while Ang-2 expression is restricted. In cancer patients, Ang-2 level is elevated, which correlates with poor prognosis. Ang-2 not only drives tumor angiogenesis but also attracts infiltration of myeloid cells. The latter rapidly differentiate into tumor stromal cells that foster tumor angiogenesis and progression, and weaken the host’s anti-tumor immunity. Moreover, through integrin signaling, Ang-2 induces expression of matrix metallopeptidases (MMPs) to promote tumor cell invasion and metastasis. Many oncogenic viruses induce expression of Ang-2 to promote development of neoplasia associated with viral infection. Multiple Ang-2 inhibitors exhibit remarkable anti-tumor activities, further highlighting the importance of Ang-2 in cancer development.

show abstract

Faricimab for treatment of diabetic macular oedema

Kovacova

2022

Practical Diabetes

View full text Add to dashboard Cite

Tie-2/Angiopoietin pathway modulation as a therapeutic strategy for retinal disease

Cited by 84 publications

References 50 publications

Targeting Angiopoietin in Retinal Vascular Diseases: A Literature Review and Summary of Clinical Trials Involving Faricimab

Targeting Angiopoietin in Retinal Vascular Diseases: A Literature Review and Summary of Clinical Trials Involving Faricimab

Role of Angiopoietins in Development of Cancer and Neoplasia Associated with Viral Infection

Faricimab for treatment of diabetic macular oedema

Contact Info

Product

Resources

About