PubMed Health⌕ Search
Home/Archive/PubMed

PubMed · 16935215

Potential future targets for treating ocular neovascularization.

Fina C Barouch·Joan W Miller
View original source ↗Export metadata ↓

Abstract

A wide variety of mediators likely contribute to ocular NV and these can serve as potential targets for the treatment of ocular NV. Several targets have already been validated in preclinical models and are being explored in clinical studies. In addition, targeting other processes besides angiogenesis, such as inflammation and apoptosis, may be beneficial in the treatment of ocular NV. Combined approaches with the use of several angiogenesis inhibitors or anti-inflammatory agents may show synergistic effects in treating ocular NV.

Explore related subjects

Angiogenesis InhibitorsAnimalsCell SurvivalDisease ProgressionEndothelium, VascularEye DiseasesHumansNeovascularization, PathologicTreatment OutcomeJournal ArticleResearch Support, Non-U.S. Gov'tReview

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Fina C Barouch, Joan W Miller. 2006. Potential future targets for treating ocular neovascularization.. https://doi.org/10.1016/j.ohc.2006.05.004

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

PubMed2007

The immunosuppressant FTY720 inhibits tumor angiogenesis via the sphingosine 1-phosphate receptor 1.

FTY720, a sphingosine 1-phosphate (S1P) analog, acts as an immunosuppressant through trapping of T cells in secondary lymphoid tissues. FTY720 was also shown to prevent tumor growth and to inhibit vascular permeability. The MTT proliferation assay illustrated that endothelial cells are more susceptible to the anti-proliferative effect of FTY720 than Lewis lung carcinoma (LLC1) cells. In a spheroid angiogenesis model, FTY720 potently inhibited the sprouting activity of VEGF-A-stimulated endothelial cells even at concentrations that apparently had no anti-proliferative effect. Mechanistically, the anti-angiogenic effect of the general S1P receptor agonist FTY720 was mimicked by the specific S1P1 receptor agonist SEW2871. Moreover, the anti-angiogenic effect of FTY720 was abrogated in the presence of CXCR4-neutralizing antibodies. This indicates that the effect was at least in part mediated by the S1P1 receptor and involved transactivation of the CXCR4 chemokine receptor. Additionally, we could illustrate in a coculture spheroid model, employing endothelial and smooth muscle cells (SMCs), that the latter confer a strong protective effect regarding the action of FTY720 upon the endothelial cells. In a subcutaneous LLC1 tumor model, the anti-angiogenic capacity translated into a reduced tumor size in syngeneic C57BL/6 mice. Consistently, in the Matrigel plug in vivo assay, 10 mg/kg/d FTY720 resulted in a strong inhibition of angiogenesis as demonstrated by a reduced capillary density. Thus, in organ transplant patients, FTY720 may prove efficacious in preventing graft rejection as well as tumor development.

Angiogenesis Inhibitors↗