COCO/DAND5 inhibits developmental and pathological ocular angiogenesis

The WWC protein family is an upstream regulator of the Hippo signalling pathway that is involved in many cellular processes. We examined the effect of an endothelium-specific WWC1 and/or WWC2 knock-out on ocular angiogenesis. Knock-outs were induced in C57BL/6 mice at the age of one day (P1) and evaluated at P6 (postnatal mice) or induced at the age of five weeks and evaluated at three months of age (adult mice). We analysed morphology of retinal vasculature in retinal flat mounts. In addition, in vivo imaging and functional testing by electroretinography were performed in adult mice. Adult WWC1/2 double knock-out mice differed neither functionally nor morphologically from the control group. In contrast, the retinas of the postnatal WWC knock-out mice showed a hyperproliferative phenotype with significantly enlarged areas of sprouting angiogenesis and a higher number of tip cells. The branching and end points in the peripheral plexus were significantly increased compared to the control group. The deletion of the WWC2 gene was decisive for these effects; while knocking out WWC1 showed no significant differences. The results hint strongly that WWC2 is an essential regulator of ocular angiogenesis in mice. As an activator of the Hippo signalling pathway, it prevents excessive proliferation during physiological angiogenesis. In adult animals, WWC proteins do not seem to be important for the maintenance of the mature vascular plexus.

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PFKFB3: A Potential Key to Ocular Angiogenesis

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.628317 ◽

2021 ◽

Vol 9 ◽

Author(s):

Zi-Yi Zhou ◽

Lin Wang ◽

Yu-Sheng Wang ◽

Guo-Rui Dou

Keyword(s):

Cell Metabolism ◽

Current Treatment ◽

Potential Treatment ◽

Ocular Angiogenesis ◽

Pathological Angiogenesis ◽

Novel Treatment ◽

Promising Target ◽

Long Time ◽

New Evidence ◽

Endothelial Cell Metabolism

The current treatment for ocular pathological angiogenesis mainly focuses on anti-VEGF signals. This treatment has been confirmed as effective despite the unfavorable side effects and unsatisfactory efficiency. Recently, endothelial cell metabolism, especially glycolysis, has been attracting attention as a potential treatment by an increasing number of researchers. Emerging evidence has shown that regulation of endothelial glycolysis can influence vessel sprouting. This new evidence has raised the potential for novel treatment targets that have been overlooked for a long time. In this review, we discuss the process of endothelial glycolysis as a promising target and consider regulation of the enzyme 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase as treatment for ocular pathological angiogenesis.

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Selective targeting and photocoagulation of ocular angiogenesis mediated by a phage-derived human antibody fragment

Nature Biotechnology ◽

10.1038/13679 ◽

1999 ◽

Vol 17 (10) ◽

pp. 984-988 ◽

Cited By ~ 82

Author(s):

Manfred Birchler ◽

Francesca Viti ◽

Luciano Zardi ◽

Bernhard Spiess ◽

Dario Neri

Keyword(s):

Antibody Fragment ◽

Human Antibody ◽

Ocular Angiogenesis ◽

Selective Targeting

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Ocular Angiogenesis

Ocular Therapeutics ◽

10.1016/b978-012370585-3.50023-6 ◽

2008 ◽

pp. 473-493

Author(s):

JING CHEN ◽

LOIS E.H. SMITH

Keyword(s):

Ocular Angiogenesis

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The role of hypoxia-inducible factors in neovascular age-related macular degeneration: a gene therapy perspective

Cellular and Molecular Life Sciences ◽

10.1007/s00018-019-03422-9 ◽

2019 ◽

Vol 77 (5) ◽

pp. 819-833 ◽

Cited By ~ 6

Author(s):

Parviz Mammadzada ◽

Pablo M. Corredoira ◽

Helder André

Keyword(s):

Gene Therapy ◽

Macular Degeneration ◽

Clinical Phenotype ◽

Therapeutic Strategies ◽

Age Related Macular Degeneration ◽

Hypoxia Inducible Factors ◽

Ocular Angiogenesis ◽

Gene Therapies ◽

Age Related

AbstractUnderstanding the mechanisms that underlie age-related macular degeneration (AMD) has led to the identification of key molecules. Hypoxia-inducible transcription factors (HIFs) have been associated with choroidal neovascularization and the progression of AMD into the neovascular clinical phenotype (nAMD). HIFs regulate the expression of multiple growth factors and cytokines involved in angiogenesis and inflammation, hallmarks of nAMD. This knowledge has propelled the development of a new group of therapeutic strategies focused on gene therapy. The present review provides an update on current gene therapies in ocular angiogenesis, particularly nAMD, from both basic and clinical perspectives.

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