CD93 as a Potential Target in Neovascular Age‐Related Macular Degeneration

Abstract

In patients with age-related macular degeneration (AMD), choroidal neovascularization is the major cause of severe visual loss. In these patients, the persistence of neovascular growth despite vascular endothelial growth factor-A blockage needs the discovery of new endothelial cell targets. The glycoprotein CD93, highly expressed in activated endothelial cells, has been recently involved in the regulation of the angiogenic process both as transmembrane and soluble protein. Choroidal neovascular membranes from patients affected by AMD were examined by immunofluorescence using anti-CD93 and anti-von Willebrand factor antibodies. Blood vessels within intraocular and extraocular neoplasias were used as controls for CD93 expression. All choroidal neovascular membranes displayed strong CD93 staining in the von Willebrand factor-positive endothelial cells, consistently with the analyses showing a high colocalization coefficient in the blood vessels. Intraocular and extraocular tumor vessels showed similar results, whereas the normal choroid displayed blood vessels with only faint CD93 staining. Additionally, the concentration of soluble CD93 was determined in the aqueous humor of patients affected by naïve neovascular AMD by enzyme-linked immunosorbent assays. Age-matched cataract patients served as controls. Soluble CD93 was significantly increased in the aqueous humor of naïve neovascular AMD patients and tended to decrease after treatment with an antiangiogenic drug. In conclusion, both transmembrane and soluble CD93 are overexpressed in patients with neovascular AMD, indicating that CD93 may represent a potential new antiangiogenic target in the treatment of choroidal neovascularization. J. Cell. Physiol. 232: 1767-1773, 2017. © 2016 Wiley Periodicals, Inc.

TGF-β concentrations and activity are down-regulated in the aqueous humor of patients with neovascular age-related macular degeneration

“…This correlation was observed in both controls and patients at baseline, but was not apparent after treatment. This may be explained by the cross-talk between the VEGF-A and TGF-β signaling pathways, although not yet completely elucidated 4 , 33 . Ranibizumab might also change the aqueous molecular constitution via VEGF-A antagonism, thus rendering such a TGF-β pathway less directly dependent on TGF-β levels.…”

C‐type lectin domain group 14 proteins in vascular biology, cancer and inflammation

“…This high expression profile was later confirmed at the protein level and correlated with poorer survival [156]. Upregulated vascular expression of CD93 has also been described in nasopharyngeal carcinoma, as well as tumours of the eye including retinoblastoma and choroidal melanoma [157,158], and correlates with a worse survival outcome. More recently, the CD93 CTLD has been derived from Escherichia coli expression systems that allow disulfide bond formation and has been purified to homogeneity allowing preliminary structural analyses using nuclear magnetic resonance approaches [159].…”

The Binding of CD93 to Multimerin-2 Promotes Choroidal Neovascularization

“…CNV membranes were collected during submacular surgery as previously described. 8 Patients were treated after being informed of the nature of the treatment being offered and the potential risks, benefits, adverse effects, and possible treatment outcomes. All patients signed consent forms.…”

“…Samples were processed as previously described. 8 , 21 Immunofluorescent staining was performed with antibodies against human Multimerin-2 22 and human CD34 (QBEnd/10; Ventana Medical Systems, Inc., Oro Valley, AZ, USA). Mouse laser-injured choroids were flatmounted and stained with anti-C1qR1/CD93 (R&D Systems, Minneapolis, MN, USA) and anti-Pecam-1 (H-3; Santa Cruz Biotechnology, Dallas, TX, USA) antibodies.…”