Optic gliomas are
brain tumors characterized by slow growth, progressive loss of vision, and limited therapeutic options.
Optic gliomas contain various amounts of myxoid matrix, which can represent most of the
tumor mass. We sought to investigate
biological function and
protein structure of the myxoid matrix in
optic gliomas to identify novel therapeutic targets. We reviewed histological features and clinical imaging properties, analyzed vasculature by immunohistochemistry and electron microscopy, and performed liquid chromatography-mass spectrometry on
optic gliomas, which varied in the amount of myxoid matrix. We found that although subtypes of
optic gliomas are indistinguishable on imaging, the microvascular network of pilomyxoid
astrocytoma, a subtype of
optic glioma with abundant myxoid matrix, is characterized by the presence of endothelium-free channels in the myxoid matrix. These
tumors show normal perfusion by clinical imaging and lack histological evidence of
hemorrhage organization or
thrombosis. The myxoid matrix is composed predominantly of the
proteoglycan versican and its linking
protein, a vertebrate
hyaluronan and
proteoglycan link protein 1. We propose that pediatric
optic gliomas can maintain blood supply without endothelial cells by using invertebrate-like channels, which we termed primitive myxoid vascularization. Enzymatic targeting of the
proteoglycan versican/
hyaluronan and
proteoglycan link protein 1 rich myxoid matrix, which is in direct contact with circulating blood, can provide novel therapeutic avenues for
optic gliomas of childhood.