Chondroitin sulfate enhances the barrier function of basement membrane assembled by heparan sulfate.

Overview

Glycosaminoglycans (GAGs) are ubiquitously expressed polysaccharides attached to proteoglycans. Here we showed that ablation of heparan sulfate (HS) polymerase Ext1 in retinal progenitor cells did not affect initial progression of retinal angiogenesis, but it disrupted the pruning of blood vessels and establishment of arterioles and venules. In the absence of retinal HS, blood vessels were also vulnerable to high oxygen tension in early postnatal stages, which can be rescued by exogenous VEGF, consistent with the role of retinal HS in the fine-tuning of VEGF signaling. Furthermore, we observed that the retinal inner limiting membrane (ILM) was disrupted by deletion of Ext1 in a timing specific manner, suggesting that retinal HS is required for the assembly but not the maintenance of the basement membrane. Lastly, we showed that further deletion of C4st1, a CS sulfation enzyme, did not affect the assembly of the ILM, but when combined with Ext1 deletion, it aggravated the retinal permeability by disrupting the retinal glycocalyx. These results demonstrated an important role of CS and HS in establishing the barrier function of the extracellular matrix.