New approaches
Leigh Spielberg
Published: Saturday, April 1, 2017
It is suspected that if we can prevent the pericytes from contacting the endothelial cells, they will remain vulnerable to anti-VEGF treatment because they will not matureNON-RESPONDERS But why are there eyes that seem to be anti-VEGF non-responders? A subset of neovascular vessels are ‘mature’. Stable vessels have associated pericytes or smooth muscle cells and a complete basement membrane, which means that they have become differentiated vessels. These mature, stable vessels are maintained via interaction between endothelial cells and pericytes. The endothelial cells generate platelet-derived growth factor (PDGF), which induces the migration of pericyte precursors. Pericyte coverage leads to inhibition of endothelial cell proliferation and production of basement membrane, which make neovascular vessels less vulnerable to anti-VEGF-induced disruption. Dr D’Amore showed colourised optical coherence tomography-angiography images of large neovascular membranes at baseline and at weeks 4, 6 and 8 during anti-VEGF treatment. “We can see from these images that, although much of the neovascularisation disappears from view, a large component of the vasculature remains, despite the presence of VEGF neutralisation,” she said. “It is suspected that if we can prevent the pericytes from contacting the endothelial cells, they will remain vulnerable to anti-VEGF treatment because they will not mature,” said Dr D’Amore. Pericytes also promote endothelial cell survival through chemical signalling and physical interactions, including production of VEGF by pericytes. Platelet-derived growth factor B (PDGF-B) is the target of a molecule called pegpleranib, developed by Ophthotech Corp. as Fovista®. Patricia A D’Amore: patricia_damore@meei.harvard.edu
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